The effects of caffeine on the electrophysiological properties of CA1 pyramidal neurones were investigated in the rat hippocampal slice preparation in vitro. A concentration-dependent increase in both the extracellularly recorded excitatory postsynaptic potential (e.p.s.p.) and the population spike resulting from stimulation of the stratum radiatum could be evoked by caffeine with a threshold concentration of 10 microM. Intracellular recordings demonstrate a caffeine-evoked decrease in resting membrane potential, an increase in input resistance, a reduction of the long afterhyperpolarization (a.h.p.) and a decrease in accommodation. The interaction between caffeine and adenosine was investigated on the extracellularly recorded e.p.s.p. The maximal response evoked by caffeine was increased in the presence of adenosine and the adenosine concentration-response curve was shifted to the right in a parallel fashion in the presence of caffeine. It is suggested that the effects of caffeine on hippocampal neurones may be mediated by a decrease of one or more potassium conductance(s), and that adenosine and caffeine may compete for the same electrophysiologically active receptor site on these cells.