The motor cortex displays remarkable plasticity in response to changes in sensory and motor experience; however, the synaptic mechanisms underlying functional plasticity are not known. It is believed that synaptic processes that alter the strength of neuronal connections, such as long-term potentiation (LTP), are mechanisms by which synaptic circuits are modified by experience, resulting in functional adaptations. In the present study, we examined the mechanisms of LTP of synaptic responses in layers II/III to vertical (stimulation in layers V/VI) and horizontal (stimulation in layers II/III) inputs, in slices from rat motor cortex. Tetanic stimulation in layers V/VI or II/III induced LTP in 60% of the field potentials (n = 20) and in 73% of the intracellularly recorded postsynaptic potentials (n = 33). LTP was induced in cells with firing patterns characteristic of regular-spiking, fast-spiking, or bursting cells. LTP was expressed, for the most part, in kainate/AMPA receptor-mediated responses; however, potentiation of NMDA receptor-mediated components was also observed. Induction of LTP was prevented when either NMDA receptors or dihydropyridine-sensitive Ca2+ channels (DSCCs) were blocked, although blockade of DSCCs was less effective in preventing LTP induction. Based on the present data and previous LTP studies, we suggest that in many forms of LTP more than one mechanism participates in the induction process. The present findings may be relevant to the synaptic mechanisms underlying functional plasticity in motor cortex.