The membrane permeable cyclic AMP analogue dibutyryl cAMP was found to have a biphasic effect on the amplitude of population spikes recorded in area CA1 of rat hippocampal slices in response to 0.05 Hz stimulation of the Schaffer collateral/commissural path. While dbcAMP was present the population spike was depressed and after washout of dbcAMP the population spike showed potentiation lasting at least 2 h. The population excitatory postsynaptic potential (EPSP) was unaffected. Addition of picrotoxin throughout the experiment caused no change in the depression but reduced the potentiation caused by dbcAMP. We conclude that cAMP may play a role in long-term potentiation (LTP).