Issue with users emails coming in from our second domain getting rejected

We are running exchange 2010 and have 1 exchange enviroment and we have users from a second domain that also have their email on our exchange system. What is happening is that the users inbound email keeps getting rejected by the spam filter.
We have  the domain in exchange setup as a accepted domain. Our spam filter group says that there is nothing wrong on that side and they are saying that it looks like an AD issue.
So I am not sure what to check either something on the exchange server or possibly some type of AD issue?
Any help would be apprciated.
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Miguel Angel Perez MuñozCommented:
Could you paste response from your spam filter? It is possible your secondary domain is not correctly setup? (any mx record missing or not correctly setup secondary domain on your spam filter?
vmichAuthor Commented:
The strange thing here is that users who are and have been part of the second domain are not having the issue. It is users that belong to the first domain(main domain) and then have their default smtp changed from the first domain to the second domain.. (ex:first smtp default domain abc123 and then change the users default to second domain def456)
This is the error message that users get when trying to send emails to these users who have had their default smtp changed to the second domain... Reason: Remote SMTP server has rejected address
 Diagnostic code: smtp;550 5.1.1 then is says that this is not a valid mailbox.....
Miguel Angel Perez MuñozCommented:
Have you updated your GAL/OAB before this change?
It is possible you are sending to old domain after change and those accounts have not got this domain associated.
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vmichAuthor Commented:
That I am not sure about...
Is there something I need to do with the GAL/OAB?
Miguel Angel Perez MuñozCommented:
From powershell:

Get-GlobalAddressList | Update-GlobalAddressList
Get-OfflineAddressBook | Update-OfflineAddressBook

Mine requires some time to finish.
vmichAuthor Commented:
Will this affect any users while this is going on and once I do this do I have to do anything to the users outlook or will they update them selves?
Miguel Angel Perez MuñozCommented:
This only refresh your newly created users, let to Outlook users access to new created users.

When you do commands from powershell, restart Microsoft Exchange File Distribution service on Exchange server, then reload GAL on Outlook (tools, send receive, download global address book)
vmichAuthor Commented:
does not exchange update this own it's own from time to time?
None of these users are really new they just had their smtp default changed.
Miguel Angel Perez MuñozCommented:
By default, every day.
Marking your internal emails as non existent must be, or users has not this domain configured or your server not recognizes as local domain.
vmichAuthor Commented:
Not sure on what you just said??
Could you explain that again?
Gareth GudgerSolution ArchitectCommented:
I was reading this line.

then have their default smtp changed from the first domain to the second domain.. (ex:first smtp default domain abc123 and then change the users default to second domain def456)

It sounds like something happened to your Email Address Policies. Someone changed it and it gave all existing users the new domain as there primary domain.

I would go to EMC >> Organization >> Hub Transport >> Email Address Policies.

First, how many policies do you have configured here? And second, can you post a screenshot?

My guess is that you only have one (the Default) and someone specified the new domain as the Primary SMTP address, which changed all users.
vmichAuthor Commented:
Thanks to all for your responses but the issue ended up being related to a virus on 1 computer which caused the email address to get on some blacklist.

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vmichAuthor Commented:
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