Some Internet providers have recently started blocking port 25, your PC port used for the transmission of mail, in an attempt to help prevent direct to MX spamming, and abuse of open proxies / relays from their dialup and broadband customers.
Some major ISPs that do this (and the address of their SMTP server) are:
People PC (mail.peoplepc.com)
Cox (smtp.west.cox.net and smtp.east.cox.net)
Unfortunately a side-effect of this practice is that it prevents users from accessing our SMTP servers. If you are getting error messages when you try sending mail which state that smtp.domain.com is not responding or not found, contact your ISP, and find out if they are blocking port 25. If they are, you can probably send outgoing mail through their outgoing mail servers. Ask your ISP for Outgoing Mail setup instructions to use their SMTP servers.
Sometimes, however, an ISP will not allow email to be sent through their SMTP server with a different domain. In other words, you may only be able to use their SMTP server if you have your reply address set to your ISP-based email address, not your custom domain name address that you have through our mail-servers.