If you are using RIA Services or just plain old WCF you and you have more than one url that you use to access your website and use IIS 6 you will need to modify your web.config file.
In my example, I access the same IIS web site using two different host headers because I have a small web farm and I want to be able to check each server in the farm after a deployment, not just use the load balanced url.
This means that I have two urls, one for load balancing that everyone uses, and the one I use for testing to make sure a particular server in the farm is working.
Here is the change I had to make to my web.config on the first server.
<serviceHostingEnvironment aspNetCompatibilityEnabled="true" >
<add prefix="http://myapp:8888" />
<add prefix="http://myapp:18888" />
This is one of the better references I have found for getting RIA Services and WCF running under .Net 3.x, IIS 6, etc.