The influence of the change of potassium and calcium concentrations in the medium bathing hippocampal slices has been tested on the purinergic drug effects. 2. The depressive effect of purinergic agonists were antagonized by 50% by doubling the potassium concentration, while they were not affected by doubling calcium concentrations. 3. The data demonstrate a direct intrinsic activity of potassium ions, and suggest a possible direct interaction between adenosine receptors and potassium transneuronal fluxes.