MS ISA Server Team blogged about a troubleshooting for ISA Server to send and receive e-mails. It's not Exchange specific but it's good to know.
There are many reasons for a published SMTP Server via ISA Server fails to receive or send emails. While troubleshooting this type of issue it is important to review the basic configuration before move further on a more deep troubleshoot, many times the root cause of the problem is much simple then you might think. This post will expose a common scenario where it was not possible to receive or send emails through ISA Server.
The topology of this scenario is based on an SMTP Publishing rule on ISA server, first deployment, in order words: this setup never worked. Internal users were unable to receive email from the Internet, although they were able to send emails to external users.