There are so many possible reasons why this might be happening that it's basically impossible to offer any kind of sensible diagnosis without more information. The most likely scenario is a change at the ISP's end, perhaps in some form of blacklist or configuration.
The best thing you can do at this point is to generate a TCP/IP session log in WinPMail - go into Tools|Internet Options and check the "Create Internet Session logs" checkbox at the bottom of the dialog; then try a connection and get the error. The session log will be a file in your mailbox directory in the form TCPXXXX.WPM. Copy the text from the file and paste it into a reply here so I can see it (make sure you obscure any password information using "x"s when you do this). Finally, remember to turn off session logging once you're done - it eats disk space quickly.
Cheers!
-- David --