The whole-cell configuration of the patch-clamp technique was used to study membrane responses of mouse Schwann cells in organotypique culture to external application of adenosine 5'-triphosphate (ATP). ATP induced an inward current (IATP) which caused a membrane depolarization. IATP was dose dependent with a Kd of 8.4 mM. ATP analogues had the following relative agonist potency: ATP > ADP approximately alpha-beta methylene ATP. Neither AMP nor adenosine were effective. IATP was reversibly reduced by suramin, a P2 purinoceptor antagonist. Alteration of ionic gradients showed that ATP activated simultaneously cationic (potassium and calcium) and anionic (chloride) conductances. Values of the reversal potentials to ATP suggested the following permeability sequence through the anion channel: SCN- > I- > Br- approximately Cl- > aspartate > isethionate. IATP did not appear to be dependent on intracellular calcium, as inclusion or omission of calcium chelator (BAPTA, 10 mM) in the pipette solution had no effect on IATP. The observed ATP response resembles a P2-mediated response in its kinetics, its relative agonist potency and its blockade by suramin, but differs from known ones by its requirement for high concentrations of ATP and the activation of a cationic as well as an anionic conductance.