The involvement of N-methyl-D-as-partate (NMDA) and non-NMDA glutamate receptors in mediating the excitatory responses of neurons in the primary motor cortex (MI) to electrical stimulation of the supplementary motor area (SMA) and the somatosensory cortex (SI) was examined in monkeys performing a trained motor task. During the task, a total of 109 MI neurons were identified and classified as movement related (91), motor set related (7), or mixed (11). Subsequently, the influence of receptor antagonists on the stimulus-evoked and task-related activities of these neurons was examined. The selective NMDA antagonist D-2-amino-5-phosphonovaleric acid (APV) and the selective non-NMDA antagonist 6-cyano-7-nitroquinoxa-line-2, 3-dione (CNQX) were applied iontophoretically through multibarreled micropipettes. One barrel was used for extracellular unit recording. The excitatory response evoked by SI stimulation was suppressed by CNQX in the vast majority (83%) of the motor task related neurons, and only 10% were suppressed by APV. On the other hand, the response evoked by SMA stimulation was suppressed by APV in 56% of the neurons and by CNQX in 54%. APV and CNQX had parallel effects on the stimulus-evoked responses and the task-related neuronal activity. These results indicate that NMDA and non-NMDA receptors are both involved in mediating the excitatory responses of MI neurons to input from the SMA and SI. On the other hand, the data suggest a greater contribution of non-NMDA receptors in response to SI input and greater involvement of NMDA receptors in mediating the response to SMA input, especially among set-related MI neurons.