You may have trouble sending mail to certain domains while using Exchange Server 2007 on Windows Server 2008. The Queue Viewer displays the following status error for the domain in question:
“451 4.4.0 primary target IP address responded with “4220.127.116.11 unable to connect.”attempted failover to alternate host, but that did not succeed.Either there are no alternate hosts, or delivery failed to all alternate hosts.”
This problem occurs because routers do not support the TCP autotuning settings in Windows Server 2008.
To disable autotuning, follow these steps:
Run CMD as Administrator
At the command prompt, type the following command, and then press ENTER:
netsh interface tcp set global autotuninglevel=disabled
This command disables the Receive Window Auto-Tuning feature.
Exit the Command Prompt window.
Restart the computer.