The effects of the epileptogenic agent, penicillin, on excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) were studied in the hippocampal in vitro slice preparation. The actions of penicillin were compared to those of bicuculline, an antagonist of γ-aminobutyric acid. Neither substance enhanced monosynaptic EPSP amplitude in CA1 pyramidal cells, but both penicillin and bicuculline depressed IPSPs. Large depolarizations that gave rise to cellular bursting activity did develop after addition of penicillin or bicuculline to the bathing medium. There was also an increase in the incidence of fast prepotentials or ‘d-spikes’. These observations are interpreted according to the hypothesis that penicillin and bicuculline block cellular IPSPs, and consequently allow remote intrinsic excitatory events to invade the cell soma and trigger action potentials.