Blocking port 25. Many large ISPs now block data between clients and MX servers when the data uses port 25.
They do this in such a manner that MX to MX SERVER traffic flows without being blocked, but client to MX server traffic is blocked. That is why the IETF made it mandatory for ISPs to open port 587 which is now the alternative SMTP port for CLIENT to MX server data transfer.
You may also have a situation where there is a core router in the path, between your client and the MZ server which cannot auto-resize MTU packet sizes.
This has become a very frequent issue, and is very hard to both diagnose and resolve, because neither you, nor the receiving MTA are responsible for the failing device, and most transport providers won't even begin to acknowledge equipment problems brought to their attention by "outsiders."
On-the-fly MTU size changes are very frequently employed, by the likes of Comcast, and other providers who initiate a connection at an MTU of 1492, and then, after the handshakes and protocols are established, bump the MTU up to 1500 to complete the data transmission.
Given the volume of e-mail data large ISPs handle in a single day, they can "squeeze" the equivalent of several additional hours of bandwidth time into a circuit by jumping to the higher MTU after establishing the connection.
Unfortunately, many legacy routers have issues with the MTU size bumps, as do some NIC cards, and even some legacy software and firewalls. Google for MTU checking software, and run some tests to check the data route. The results may prove eye opening.
You should also make certain port 587 is properly setup and bound in SmarterMail, and have your POP, SMTP, IMAP and DELIVERY LOGS all set to detailed, keeping them for at least six months so you can go back and check new issues against old traffic to spot trouble patterns.
(We keep all of our detailed logs at least 60 months).
EDIT NOTE: Spelling corrected and reformatted. Originally posted via browser on Android device.
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