The adenosine receptor binding enhancer, PD 81,723, enhances the inhibitory effects of exogenously applied adenosine in a dose-dependent manner in hippocampal brain slices. Extracellular recordings were obtained from the CA1 cell layer while electrically stimulating the stratum radiatum. Application of 1, 10 or 32 microM PD 81,723 in the presence of adenosine resulted in a dose-dependent reduction in the amplitude of the population spike which could be partially reversed by theophylline. In addition, hippocampal slices exposed to adenosine showed greater paired-pulse facilitation compared to control and this facilitation was significantly enhanced by the presence of PD 81,723. PD 81,723 had no effect when administered alone, but required the presence of adenosine. These results demonstrate that in addition to enhancing adenosine receptor binding, PD 81,723 also enhances the functional activity of adenosine in the hippocampal slice.