FMRFamide (phenylalanyl-methionyl-arginyl-phenylalanine amide) is a cardioexcitatory peptide recently isolated and identified in molluscan ganglia. Both FMRFamide and 5-hydroxytryptamine (5HT), the cardioexcitatory neurotransmitter in molluscs, were tested on the ventricle of the bivalve Mercenaria mercenaria. Both agents increased myocardial contractility, the intracellular cyclic AMP concentration of intact hearts and the adenylate cyclase activity of a myocardial membrane fraction. FMRFamide was 5--10 times more potent than 5HT. All of the effects of 5HT, and none of those of FMRFamide, were blocked by methysergide, a specific 5HT antagonist.