The two-electrode voltage-clamp technique was used to study the ionic basis of the slow depolarization caused by the neuropeptide proctolin. At negative membrane potentials, proctolin caused a dose-dependent slow inward current. This current reversed and became outward at membrane potentials positive to 0 to +20 mV. Current-voltage curves also showed the response to be voltage-dependent, with a reversal potential at positive membrane potentials. The response was blocked in sodium-free solutions. Solutions with reduced sodium concentration caused a shift of the reversal potential in a manner expected for a response that is largely sodium-dependent. We conclude that proctolin causes an inward current by increasing a voltage-dependent cation conductance that is predominantly permeable to sodium.