The effects of the phorbol ester 4 beta-phorbol-12,13 dibutyrate (PDBu) and the protein kinase (PK) inhibitors H-7 and sphingosine were investigated on the short-term potentiation (STP) of the population excitatory postsynaptic potential (EPSP) induced by perfusion of N-methyl-D-aspartate (NMDA) in the stratum radiatum of CA1 of the rat hippocampal slice. Bath perfusion of 130 microM NMDA for 10 s caused an initial depression of the population EPSP followed by a STP, which averaged 46% and lasted 16 min. PDBu (100 nM) perfused for 2 h completely inhibited the NMDA induced STP, suggesting that the stimulation of PKC inhibited an NMDA receptor activated process which induced the STP. The protein kinase inhibitors H-7 and sphingosine did not alter the NMDA induced STP.