Substance P, a naturally occuring polypeptide of mammalian origin, has been implicated both as a neurotransmitter and a neurohormone. However, little is known of the ionic mechanisms underlying the postsynaptic response to substance P. In myenteric neurones Katayama and North reported substance P-evoked depolarisations (of varying latency) associated, surprisingly, with a decrease in membrane conductance. A direct measurement of reversal potential in normal ionic conditions was not achieved but it was suggested that substance P acts by reducing membrane potassium conductance. In contrast, work on salivary glands suggests that substance P evokes an increase in potassium conductance; however,electrophysiological work has not been carried out to verify this. We report here that substance P evokes a marked increase in rat parotid acinar cell membrane conductance associated with a potential change (latency 1.7 s) that reverses at about --65 mV. The reversal potential for substance P is shown to be identical to that obtained in the same cells for acetylcholine (ACh) and adrenaline. The identical membrane action of ACh, adrenaline and substance P, mediated by three separate receptor sites, suggests activation of a common effector mechanism.