I'm going to assume that you are not using Windows Small Business Server (SBS) and, therefore, ISA Server is not playing a part in this. There is a fantastic tool called SmtpDiag.exe available for download from Microsoft. It will help you identify why inbound email is not being accepted. If your external MX records were altered, it could cause telnet and other hosts to point at the wrong server.
Since you mentioned that you were just the victim of an open SMTP relay from a spammer, you'll also want to make sure that your outbound email is not adversely affected. You can check to see if your SMTP host IP address is on a blocklist at Spamhaus.
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This was first published in September 2008