It has been established that ATP is released from motor nerve terminals and that exogenous ATP depresses end-plate potential (e.p.p.) amplitudes. This study assessed whether presynaptically released ATP reduced e.p.p.s. E.p.p.s in the rat extensor digitorum longus muscle were depressed by exogenous ATP and adenosine. If ATP hydrolysis to adenoisine was blocked, however, ATP had no effect. Addition of theophylline increased e.p.p. amplitude due to removal of the depressant effect caused by ATP contained in the quantal release. This inhibition was absent when the rate of release was reduced by high Mg2+. It is concluded that e.p.p. inhibition is mediated by adenosine derived from presynaptically released ATP.