Adenosine was found to decrease the amplitude of presynaptic fiber spikes recorded in stratum radiatum of the CA1 region of the hippocampus following stimulation of the Schaffer collateral and commissural afferents. The presynaptic fiber spike reflects currents activated in the presynaptic fibers and nerve terminals of this projection. However, the effect of adenosine was largely the result of: (a) temporal overlap between the presynaptic fiber spike and the field EPSP response and (b) an indirect effect most likely related to the hyperpolarization of CA3 neurons giving rise to the Schaffer collateral fibers. When the CA3 region was separated by a knife cut from the CA1 region and the field EPSP blocked with 6,7-dinitroquinoxaline-2,3-dione, the effect of adenosine was markedly reduced, but was still significant (4.4 +/- 1.4% reduction in the amplitude of the presynaptic fiber spike). However, this action was not mimicked by the Ca2+ channel antagonist cadmium, suggesting that it did not reflect an inhibition of Ca2+ currents by adenosine. This effect was not observed in the presence of the K+ channel antagonists Ba2+ or diaminopyridine. These results suggest that adenosine may have a small hyperpolarizing effect on the presynaptic nerve terminals, but this is unlikely to be the mechanism by which adenosine modulates transmission in this brain region.