We describe here the electrophysiological characterization of a dual inhibitory action of FMRFamide (FMRFa, Phe-Met-Arg-Phe-NH2) on the caudodorsal cells (CDCs) of the pond snail Lymnaen stagnalis: (i) a transient hyperpolarizing response (H-response) and (ii) a suppression of the excitability of the cells, which lasted as long as the peptide was present. Both effects of FMRFa occurred in silent, excitable cells as well as discharging cells. The effects were reversible and dose-dependent in the range of 10-9 to 10-5 M. The H-response was not blocked by any of the antagonists to classical neurotransmitters that were tested. The reversal potential of the H-response was dependent on the [K+]o, which suggests that K+ is the major charge carrier in this response. 4-Aminopyridine (4-AP) blocked the H-response but did not affect the suppression of the excitability by FMRFa. This indicates that the effects of the peptide on these cells are independent. Experiments on the mechanism of the inhibition of the excitability indicated that FMRFa blocks the cAMP-dependent activation of the pacemaking mechanism of the CDCs. In experiments with isolated cells it was demonstrated that the actions of FMRFa are mediated directlly through receptors on CDCs (H-response: ED50 = 10-8 M). Finally, anti-FMRFa-positive varicosities and axons close to the somata, the axons and the neurohaemal endings of the CDCs were demonstrated immunocytochemically. The duality of the action of FMRFa on the neural activity of CDCs indicates its role of high priority in the regulation of egg laying behavior. © 1988.