A brief high frequency tetanic stimulation of afferent fibers induces a long-term potentiation (LTP) of synaptic transmission, which is manifested by an increase in the size of the synaptic response elicited by low frequency stimulation of the same synapse. LTP persists for several hours in vitro and up to several weeks in vivo, and is at present the most extensively studied form of activity-dependent synaptic plasticity. This article focuses on the relationship between two key elements in the induction of LTP--the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor and the Ca(2+)-phospholipid-dependent protein kinase C (PKC). In view of several recent findings that describe a direct positive modulation of NMDA currents by PKC, we suggest that PKC activity may, in fact, determine the threshold of LTP induction. Enhanced kinase activity may underlie the central role of the NMDA receptor--channel complex in neuronal plasticity.