Substance P (SP, 2.5-10 microM) was applied by rapid bath perfusion to bullfrog lumbar sympathetic neurones in vitro, voltage-clamped through a single micro-electrode. In unclamped cells, SP produced a depolarization accompanied by an increase in apparent input resistance. Under voltage-clamp a voltage-dependent inward current was induced by SP, during which the time-dependent relaxations induced by square voltage commands were inhibited. It is concluded that SP inhibits the M-current (IM), a species of voltage-dependent K+-current, and that IM-inhibition was the primary cause of the inward current and membrane depolarization in the cells tested.