You mention in an earlier post that you are going to MDP9.
MDP9 does give slightly more illuminating SMTP error messages, due to improvements in .NET 2.0.
The likely problems are:
SMTP server is no longer at the address you specified
SMTP has been disabled on the mail server
Security has been changed on the mail server, denying access to the machine via IP address, policy or user credentials.
This started on Feb 29th, worked perfectly from June '07 until then. Our network team is less than helpful. I have checked all the settings I can think of ..