Damm handy article to have in your back pocket!
Source: http://msexchangeteam.com/archive/2006/12/28/432013.aspx
From time to time, you need to allow an application server to relay off of your Exchange server. You might need to do this if you have a SharePoint, a CRM application like Dynamics, or a web site that sends emails to your employees or customers.
You might need to do this if you are getting the SMTP error message “550 5.7.1 Unable to relay”
The top rule is that you want to keep relay restricted as tightly as possible, even on servers that are not connected to the Internet. Usually this is done with authentication and/or restricting by IP address.