Are you sending on a non-standard port (ie. not 25?) If so SMTPClient doesn't run in medium trust.

http://www.west-wind.com/WebLog/posts/232833.aspx

+++ Rick ---

>We recently launched a new web site to replace our old site. We developed the new site on a second server (both are in our DMZ). When we launched the site we simply pointed our external address on the firewall to the new server, instead of the old
>One of the pages allowed users to send a secure email to us using a form on the site. I can't get it to work on the new machine. Our email server is not in the DMZ, but inside. I can telnet from the old machine into Exchange server, but not from the new machine, so I know it's not in our app code. Our network guys say that the firewall is configured to let port 25 traffic pass from either machine. I have replicated all of the IIS settings from the old machine to the new. Does anyone have any ideas on where to look from here?