Adenosine exerts prominent inhibitory effects on synaptic transmission via a presynaptic action. Using the hippocampal slice preparation, we have found in electrophysiological experiments that this action of adenosine is blocked by intrahippocampal injections of pertussis toxin. In biochemical studies, we have confirmed that this treatment affects the GTP-binding proteins, Gi and Go, in this preparation. These results indicate that both pre- and postsynaptic actions of adenosine involve pertussis toxin-sensitive GTP-binding proteins.