A reliable request-response mechanism allows a requesting computer system and a responding computer system in an established end-to-end connection to send and receive messages in a manner that the responding computer system processes a request as intended by the requesting computer system, such that all the message communication is initiated by the requesting computer system. The requesting computer system and responding computer system can accommodate a wide range of messaging failures, such as intermittent network connections or failure of a transport of SOAP intermediary by resending cached versions of previously sent messages, and by acknowledging receipt of each message received. Cached messages on either computer system are deleted after being appropriately acknowledged. After all sent messages have been acknowledged by the responding computer, and the requesting computer has received all of the response messages from the responding computer, the end-to-end connection is terminated with an exchange of connection termination messages.