A JMSReplyTo destination can be configured but it is assumed by Mule that it will be another service r external application listening on that replyTo and not the current service invocation. If a replyTo is set, the outbound router automatically makes the call asynchronous. I think the proper behaviour should be that if the endpoint is synchronous with a JMSReplyTo set, that should be used as the response channel. The endpoint would need to be asynchronous (or transacted) in order for the JMSReplyTo destination to be set and for Mule not to read directly from it