The effects of adenosine on inhibitory synaptic transmission in area CA1 were examined using the rat hippocampal slice preparation and intracellular recording. Adenosine did not change fast inhibitory synaptic potentials (IPSPs) but depressed late IPSPs evoked by direct activation of interneurons in the presence of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). Directly activated IPSPs were unchanged by the selective adenosine A1 receptor antagonist 8-cyclopentyltheophylline (CPT), but CPT reversed hyperpolarization and depression of late IPSPs produced by adenosine. These results indicate that adenosine depresses disynaptic IPSPs in area CA1 by decreasing synaptic activation of inhibitory neurons.