This study extends previous investigations into the effect of adenosine on bicuculline-resistant paired-pulse inhibition between field potentials evoked 300 ms apart in the CA1 area of the rat hippocampal slice. A direct assessment of the effect of adenosine on paired-pulse inhibition is complicated by the facts that adenosine directly depresses evoked potentials and bicuculline-resistant paired-pulse inhibition is greater between pairs of small potentials than between pairs of larger potentials. Adenosine increased biculline-resistant paired-pulse inhibition when stimulus strength was constant between adenosine and control but paired-pulse inhibition of responses in adenosine was markedly less than paired-pulse inhibition of control responses of the same size. Furthermore, adenosine decreased the size of conditioned potentials to a significantly lesser extent than unpaired potentials of the same initial size. Taken together the results indicate that adenosine can decrease bicuculline-resistant paired-pulse inhibition in the hippocampus. A possible mechanism for this effect i s that adenosine is suppressing transmission at excitatory terminals onto interneurones which would suggest that these receptors are more sensitive to adenosine than those on the Schaffer collateral/CAl pyramidal cell synapses. in this case adenosine should reduce paired-pulse inhibition at lower concentrations than are required for depression of single evoked potentials. A comparison of the concentration-response relationships for the effects of adenosine on paired-pulse inhibition and on single evoked potentials ruled out greater sensitivity of adenosine receptors at excitatory terminals onto interneurones as an explanation for adenosine's action on bicuculline-resistant paired-pulse inhibition. Adenosine was less effective at reducing inhibition evoked by large supramaximal conditioning stimuli than by stimuli submaximal for evoked potential size, although control paired-pulse inhibition is larger in the latter case. This finding is consistent with adenosine reducing bicucullineresistant paired-pulse inhibition by causing an increase in simultaneous paired-pulse facilitation.