SharePoint 2007 Outgoing E-mail Troubleshooting Tips

Tip #1

Talk to your networking/mail team and get the SMTP server address and port

Tip #2
Go to the index server and open a command prompt and use the basic old school dos command “telnet”.
telnet smtp.server.com 25
(Typically SMTP operates over port 25, but your company may be different.)
What will happen with this command is one of two things:
If it opens up and basically looks like a blank screen, that means that the SharePoint server can talk to the SMTP server fine.
If it tells you something along the lines of “connect failed”, you know that your SharePoint server can’t talk to the SMTP server. What you should then do is talk to your networking team and make sure that your SMTP server allows connections from your SharePoint server. Once that is done, retest your telnet command.

Tip #3
If your networking team says that you have the server correct, port correct and that there is no reason your server can’t connect to the SMTP, then check your SharePoint server and see if its running any antivirus. The past few clients have been running McAFee antivirus. In its Access Prevention Task, "Prevent mass mailing worms from sending mail" has been enabled and that was blocking the server from connecting to the SMTP server over port 25. As soon as I disabled that I was able to telnet in without issues and then I was able to send email from SharePoint without issue.
I am not sure about the other antivirus vendors but I am sure they have something similar, so check the settings to see if they block port 25.

Tip #4
Check to make sure that Windows Firewall is not blocking port 25, if it is, make sure that you add 25 as an exception.