1. The effects of 4-aminopyridine (4-AP) on neurotransmission in hippocampal slices of the rat were studied in vitro. 2. Extracellular recordings of field potentials and intracellular recordings of excitatory and inhibitory post-synaptic potentials, action potentials and TTX-resistant spikes were obtained from the somatic and dendritic fields of CA 1 hippocampal neurones. 3. Constant perfusion with, or bolus injection of 4-AP in micromolar concentrations resulted in substantial and persistent enhancement of the amplitude of synaptic field potentials and population spikes with no alteration of the afferent input. Somatic positive waves (p-waves) were increased with local micro-application of 4-AP. 4. Intracellular recordings revealed an increase in the amplitude of e.p.s.p.s. and i.p.s.p.s. I.p.s.p.s were prolonged by 4-AP. 5. The pyramidal cells were, after an initial hyperpolarization, depolarized by up to 10 mV during exposure to 4-AP; the membrane conductance was not consistently changed. 6. Spontaneous shifts of the membrane potential were described as giant e.p.s.p.s and i.p.s.p.s. Spontaneous i.p.s.p.s were increased in frequency and amplitude. 7. Paired-pulse facilitation of e.p.s.p.s was reduced by 4-AP suggesting a presynaptic modulation of transmitter output. 8. It is concluded that 4-AP enhances transmitter release at both excitatory and inhibitory synapses in the hippocampus.