1. Is this a site to site VPN (Router to Pix)?
a.If so what IOS on the router are you using (the flash file name)?
2. Are you using the nat (inside) 0 command on the 506 to pass IPSEC traffic?
If all these questions are yes, then an access-list somewhere (probably the outgoing access-list bound to the inside interface on the 506) is denying, at a minimum, one or more of the following ports.
TCP port 135 - Allow client to come in via MSRPC
TCP port 139 - The netbios connection. This port is the connection that is maintained during the MAPI session. If you do a netstat -a -n, you will see that you have an "established" connection to IP of mail server:139 while Outlook is open.
UDP port 137 and port 138 - used by WINS and Exchange to allow updates of new changes. (Such as new email being sent to an Outlook client's inbox).
Also, there are 2 tcp ports in the range of 1024-65536 that are used to deliver mail back from the client.
I can get more specific if this is close to your setup.
RJ
