Aqueous extracts of molluscan ganglia have cardioexcitatory activity that is not attributable to the usual neurohumors: 5-hydroxytryptamine, acetylcholine or dopamine. Morphological, physiological and biochemical studies have suggested that this cardioexcitation is caused by a handful of unidentified neurohormones, mostly polypeptides. One of the active components of extracts of the pooled central ganglia of Macrocallista nimbosa (Bivalvia) has now been isolated, purified, characterized and synthesized. This substance, previously designated peak C, is a tetrapeptide amide: phenylalanyl-methionyl-arginyl-phenylalanine amide (Phe-Met-Arg-Phe-NH2; FMRFamide). Low concentrations of FMRFamide (threshold: 10−9–10−8M) induce rhythmical activity in isolated quiescent bivalve hearts and augment the force and frequency of contraction of those already beating. The peptide also produces contractures of non-cardiac molluscan muscles, including especially the radula protractor of the whelk, Busycon contrarium, a sensitive assay object. The effects of FMRFamide on Mercenaria mercenaria hearts appear to be mediated by adenosine 3', 5'-monophosphate (cycwic AMP). Peak C activity occurs in all species tested in all the major molluscan classes; but we do not yet know whether all Peak C';s are FMRFamide. That FMRFamide is a neurosecretory product has still to be established, and its normal physiological role in molluscs has yet to be defined. Nevertheless, we suppose that, together with other neuropeptides, FMRFamide is released into the hemolymph to provide long-term maintenance and regulation of tone, rhythmicity and excitability of visceral muscle.