The present invention extends to methods, systems, and computer program products for multiplexed communication for duplex applications. Embodiments of the invention facilitate a multiplexed variant of long polling over a request/reply communication medium that (potentially significantly) reduces the resources utilized when exchanging messages. The lightweight address generation mechanism facilitates polling and routing for a pool of many clients and many services while minimizing allocated resources to each established session. Further, the benefits of a lower latency bidirectional communication medium between clients and services can be utilized.