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I have a bunch of POP/SMTP accounts that are setup on my laptop that happens to connect to an Exchange server as well. When I'm not on the network (or when I connect via VPN), I cannot send messages using SMTP. I can receive fine.
I'm using Outlook 2007 on Windows 7. However, I've witnessed this same issue on an XP machine using Outlook 2003.
1This is what I have done in the past for this to work. You could also check if your Admin has setup Outlook from Anywhere which basically makes Outlook work with your Exchange without the need of VPN. – Hondalex – 2009-11-24T14:37:56.570