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In this paper, a cross-layer design framework for multi-input multi-output (MIMO)/orthogonal frequency division multiplexing (OFDM) based wireless local area networks (WLANs) is proposed. In contrast to conventional systems where the medium access control (MAC) and physical (PHY) layers are separately optimized, our proposed methodology jointly designs a multi-packet reception (MPR) based protocol with adaptive resource allocation. Specifically, a realistic collision model is employed by taking into consideration the PHY layer parameters such as channel information, space-time coded beamforming and multiuser detection, as well as sub-carrier, bit, and power allocation. The allocation problem is formulated, so as to maximize the system throughput, subject to the constraints from both the MAC and PHY layers. These constraints depend on the results of access contention, data packetsiquest length, usersiquest spatial correlation and the quality of channel feedback information. An iterative algorithm is then provided to obtain the optimal solution. Simulation results will show that our proposed approach achieves significant improvement in system performance such as average throughput and packet delay, compared with conventional schemes where cross-layer design and optimization is not used.