We have studied the effects of staurosporine, an antagonist of the catalytic subunit of protein kinase C, on the mechanisms of long-term potentiation (LTP) in rat hippocampal slices maintained in vitro. Application of staurosporine did not affect pre-established LTP, but resulted in a decaying potentiation when high frequency stimulation was delivered in its presence. However, coactivation of two inputs to the same group of CA1 neurons during high frequency stimulation transformed the decaying potentiation into stable LTP. Staurosporine also reduced the NMDA receptor-mediated component of synaptic responses to burst stimulation. It is concluded that the PKC antagonist interferes with LTP induction, but not expression mechanisms.