The effect of penicillin on neurons of Aplysia californica was studied using drug concentrations which would be convulsant in mammalian nervous systems. Iontophoretic responses were elicited by the application of acetylcholine, dopamine, gamma-aminobutyric acid and serotonin. Low concentrations of penicillin (2 mM) consistently and reversibly reduced the chloride-dependent hyperpolarizing responses by approximately 70%, regardless of the transmitter required to evoke them. The short depolarizing responses which are sodium sensitive are slightly reduced by a much higher (10 mM) concentration. The extent of the reduction of the excitatory response varied with the transmitter. The slow sodium-dependent depolarizations and the slow potassium-dependent hyperpolarizations were unaffected by the concentrations of penicillin used. The possibility that the convulsant effect of penicillin is due to interference with membrane conductance to chloride is discussed.