1. Macroscopic and single-channel currents were recorded from voltage-clamped neurones in the abdominal and pleural ganglia of Aplysia californica in order to investigate conductance changes elicited by application of the endogenous peptide FMRFamide (Phe-Met-Arg-Phe-NH2) and related neuropeptides to the cell surface. 2. The Ca-dependent K current, IK(Ca), when elicited at a constant voltage by intracellular injection of Ca2+, was insensitive to FMRFamide or its derivative YGG-FMRFamide (Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2). 3. Under steady voltage clamp, certain cells responded to a brief puff of FMRFamide or YGG-FMRFamide with a transient outward current lasting about 1 min. Unclamped cells responded with a corresponding hyperpolarization. These responses reversed at about -75 mV. Ion substitution indicated that the current is carried by K+. 4. FMRFamide and YGG-FMRFamide were equally effective in activating the outward current, whereas FMRF, met-enkephalin and leu-enkephalin were ineffective. 5. At voltages negative to -30 mV and, in the absence of extracellular Ca2+, also at more positive potentials, the FMRFamide-sensitive current showed no voltage dependence beyond that predicted from constant-field considerations. 6. The response to FMRFamide was relatively insensitive to extracellular tetraethylammonium (TEA, KD approximately 75 mM) and 4-aminopyridine (4-AP, KD approximately 6 mM). It was suppressed in Ba-containing solutions, but was unaffected by injection of the Ca chelating agent EGTA. The response was blocked by serotonin and other agents known to elevate intracellular adenosine 3',5'-phosphate (cyclic AMP) levels, and by direct injection of cyclic AMP into the cell. 7. In its pharmacological properties and lack of voltage dependence, the FMRFamide-activated current resembles the 'S' current, IK(S), a K current suppressed by application of serotonin in Aplysia neurones. 8. The similarity between the FMRFamide-sensitive current and the 'S' current was confirmed in cell-attached patch-clamp studies, in which activity of 'S' channels was found to be reduced by serotonin, and enhanced by FMRFamide. 9. Thus, FMRFamide may function in Aplysia to counteract the serotonergic modulation of 'S' channels, which has been proposed as a mechanism of presynaptic plasticity in this mollusc.