When a host has multiple NICs, James will try to do the right thing when sending mail. In some network setups, this is not correct, and manual configuration is needed.
James requires multiple changes to fully configure how it interacts with the network. Open the config.xml file, located in $SF_HOME/apps/james/james-2.2.0/apps/james/SAR-INF/ for version 5.1.
Locate the '<mailet match="All" class="RemoteDelivery">' section. add a subnode '<bind>$addr</bind>' where $addr is the ip address that James should be sending mail from.
Near that area, there is a <servernames...></servernames> section. Confirm/change the two autodetect options (autodetect, autodetectIP) to false. Next, add the fully qualified host name, and the ip address that will be used, to their own <servername> entry.
After the changes are complete, save the config.xml and restart the application.