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Exchange 2010 SMTP response Server error: '550 5.7.1 Unable to relay'

Last Modified: 2013-11-30

I've a Exchange 2010 Server that is back to ISA Server 2006. I'va published the OWA, POP3 and Mail Server with no problems. Receive and send e-mails works fine if the Outlook is configured inside office and OWA works fine. But I need configure some machines with POP3 and SMTP. The POP3 connection works and users can receive emails but when they try to send always receive a message

Server error: '550 5.7.1 Unable to relay'

If they use in mail client the SMTP configuration with no authentication receive the message, if use a authentication the mail client enter into loop requesting the credentials but never accept. I try using DOMAIN\User, user@internetdomain.com, user@internaldomian.com and never works.

My IT environment is:

1 Domain Controller W2K8 R2
1 Excgange 2010 Mx, CAS and HUB in W2K8 R2
1 Exchange 2010 Edge in W2K8 R2
1 ISA Server 2006 SP 1 in W2K3 R2

Some information will be helpful.
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