The effects of topical or iontophoretic application of adenosine (AD) were studied by means of intracellular recording techniques in rat hippocampal slices. AD applied in a microdrop containing up to 0.1 nmol of AD produced a 7 +/- 0.7 mV hyperpolarization associated with a 30% decrease in input resistance of the recorded neurons. The hyperpolarization was dependent on the resting membrane potential and had an apparent reversal potential of about -90mV. These effect were still present when synaptic activity was blocked. AD also caused a marked reduction in the magnitude of synaptic potentials in the recorded neurons. Iontophoretic application of AD in dendritic regions caused a suppression of EPSP without affecting resting membrane potential ionotophoresis of AD onto somata produced both hyperpolarization and decreased EPSP. It is suggested that AD produces both presynaptic depression of transmitter release and postsynaptic increase in K+ conductance.