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The only thing I can think of is the preferred DNS server is correct, but the alternate may be pointing to an outside DNS server, and therefore you can't reach the internal mail server.
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Good idea but not the problem in this case...both the primary and secondary DNS listings are pointed to my internal DCs.
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Do either of these machines (client or server) have multiple nics?
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The Exchange server is virtualized and running in VMWare and we have it setup with just one NIC. &nbsp;The clients vary but I can't think of any that would have more than one NIC.
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Ok, so I did a little research and I wonder if this is your issue:<br />
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<a href="http://support.microsoft.com/kb/908521" rel="ugc nofollow">http://support.microsoft.com/kb/908521</a>
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Hmm, that doesn't look quite right to me. &nbsp;We have no problems with users on Outlook 2003/2007/2010 clients, its limited to OWA. &nbsp;In addition there are no event log errors referencing problems with the RPC service when this happens.
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Does the HTTP service stop?&gt;&gt; You will find that under Start&gt;&gt;run line&gt;&gt;type in Services.msc<br />
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we might have to go back to simple pings to see if this is a DNS related issue and DNS is not resolving to the FQDN of the mail server, or if this is a IIS and HTTP service problem. <br />
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When a client is having the issues, can he/she ping the FQDN of the mail server?
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I believe the HTTP service continues to run but it does not respond. &nbsp;I can both ping and RDP to the server when this happens but I'm using an IP rather than the name so that won't help us see if its a DNS issue. &nbsp;I can say that I don't see any DNS related errors in the event logs (or anyting else that would clue me in).<br />
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The only problem with checking this would be that I'd have to wait for it to happen again and I've been asked to fix it before that happens! &nbsp;:)<br />
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I have been reading that resetting the virtual directories may help though I'm not really seeing how it would work:<br />
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<a href="http://www.msexchange.org/tutorials/Fixing-Damaged-Incorrectly-Configured-OWA-2003-Installation.html" rel="ugc">http://www.msexchange.org/tutorials/Fixing-Damaged-Incorrectly-Configured-OWA-2003-Installation.html</a><br />
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Do you think that is worth trying?
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It's worth a try to reset the virtual directories.. But, you should have multiple failures to logon that would be noticeable if the virtual directories were a problem. <br />
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I was working on a similar post a while back: <br />
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<a href="https://www.experts-exchange.com/questions/24787387/OWA-not-passing-credentials.html" rel="ugc">https://www.experts-exchange.com/questions/24787387/OWA-not-passing-credentials.html</a><br />
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Maybe this will help. 
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Hmm, I read through most of that and the associated links but it still doesn't sound quite like the problem we're having. &nbsp;I also ran the exchange best practices analyzer tool to see if that picked up anything and it did find some problems with message store permissions (which I don't think are related) and with how the system handles the 4GB of memory we assigned it. &nbsp;The memory thing could be part of the problem so I've applied a couple of tweaks to the registry and startup files that are required for handling that much memory. &nbsp;I'm going to restart tonight and we'll see what happens. &nbsp;Thanks for all of your help so far!
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I've been experiencing a problem with my exchange server over the last few weeks. &nbsp;At what seems like random times I'm getting notifications from my monitoring software that the HTTP service on exchange is not responding. &nbsp;When this happens no one is able to log into outlook web access. &nbsp;Regular Outlook clients continue to work normally and email continues to be sent/received but no one can log into OWA. &nbsp;I've tried resetting iis and also restarting the site itself but nothing short of a full server reboot fixes this. &nbsp;It tends to appear again after two or three days. &nbsp;I can't find any clues in the event logs and there have been no recent changes to the server. &nbsp;I actually resorted to calling Microsoft for support but they won't touch it because its running in VMWare. &nbsp;I'd greatly appreciate any help with this one.
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I've been experiencing a problem with my exchange server over the last few weeks.  At what seems like random times I'm getting notifications from my monitoring software that the HTTP service on exchange is not responding.  When this happens no one is able to log into outlook web access.  Regular Outlook clients continue to work normally and email continues to be sent/received but no one can log into OWA.  I've tried resetting iis and also restarting the site itself but nothing short of a full server reboot fixes this.  It tends to appear again after two or three days.  I can't find any clues in the event logs and there have been no recent changes to the server.  I actually resorted to calling Microsoft for support but they won't touch it because its running in VMWare.  I'd greatly appreciate any help with this one.

Outlook Web Access site stops working randomly

Exchange is the server side of a collaborative application product that is part of the Microsoft Server infrastructure. Exchange's major features include email, calendaring, contacts and tasks, support for mobile and web-based access to information, and support for data storage.

Exchange

Windows Server 2003 was based on Windows XP and was released in four editions: Web, Standard, Enterprise and Datacenter. It also had derivative versions for clusters, storage and Microsoft’s Small Business Server. Important upgrades included integrating Internet Information Services (IIS), improvements to Active Directory (AD) and Group Policy (GP), and the migration to Automated System Recovery (ASR).