When the remote host is multihomed, the name-to-address translation will return a list of alternative IP addresses. As specified in Section 18.104.22.168, this list should be in order of decreasing preference. Application protocol implementations SHOULD be prepared to try multiple addresses from the list until success is obtained. More specific requirements for SMTP are given in Section 5.3.4.
When the local host is multihomed, a UDP-based request/response application SHOULD send the response with an IP source address that is the same as the specific destination address of the UDP request datagram. The "specific destination address" is defined in the "IP Addressing" section of the companion RFC [INTRO:1].
Similarly, a server application that opens multiple TCP connections to the same client SHOULD use the same local IP address for all.