Microprocessor design is undergoing a major paradigm shift towards multi-core designs, in anticipation that future performance gains will come from exploiting threadlevel parallelism in the software. To support this trend, we present a novel processor architecture called the Multiple Instruction Stream Processing (MISP) architecture. MISP introduces the sequencer as a new category of architectural resource, and defines a canonical set of instructions to support user-level inter-sequencer signaling and asynchronous control transfer. MISP allows an application program to directly manage user-level threads without OS intervention. By supporting the classic cache-coherent shared-memory programming model, MISP does not require a radical shift in the multithreaded programming paradigm. This paper describes the design and evaluation of the MISP architecture for the IA-32 family of microprocessors. Using a research prototype MISP processor built on an IA-32-based multiprocessor system equipped with special firmware, we demonstrate the feasibility of implementing the MISP architecture. We then examine the utility of MISP by (1) assessing the key architectural tradeoffs of the MISP architecture design and (2) showing how legacy multithreaded applications can be migrated to MISP with relative ease.