I was trying to figure out why I couldn't send emails from DotNetNuke using Exchange 2007 when I found a post on the DNN forums pointing to this article from the Exchange team:
http://msexchangeteam.com/archive/2006/12/28/432013.aspx
Basically, you need to enable Exchange to relay but it's not as simple as in Exchange 2003: you need to create a new SMTP receive connector and allow it to relay in a secure way. The article explains how.