Enprofylline is a novel xanthine with a low adenosine antagonistic potency, but with a good bronchodilator activity. In order to further elucidate its central nervous actions we have studied its effects in the rat hippocampus, both electrophysiologically and biochemically. Adenosine was found to depress evoked field excitatory post-synaptic potentials (EPSPs) in the rat hippocampus. The effect of adenosine was antagonized by theophylline but not by enprofylline. Both xanthines caused a slight increase per se of the field EPSP amplitude. Cyclic AMP accumulation in the rat hippocampus was stimulated by the adenosine analogue NECA, by isoprenaline and by noradrenaline in the presence of propranolol. The cyclic AMP accumulation induced by these agents was not significantly altered by omitting calcium. Enprofylline antagonized the effect of NECA and noradrenaline (after beta-blockade) but not that of isoprenaline. The IC50 of enprofylline against NECA was about 20 mumol X 1(-1). The inhibitory effect of enprofylline against NECA induced cyclic AMP accumulation was not affected by omitting calcium or by the calcium channel antagonist felodipine, but was decreased by the calmodulin inhibitor stelazine and the intracellular calcium chelator Quin-2. The results show that enprofylline is much more potent as an inhibitor of adenosine A2-receptor-mediated cyclic AMP accumulation than against adenosine A1-receptor-mediated inhibition of field EPSP. The difference may depend on a role of a special pool of calcium in the former response.