The presence of the molluscan neuropeptide FMRFamide was investigated in the heart of the sea hare, Aplysia californica. Immunohistochemical localization and high performance liquid chromatography (HPLC) coupled with radioimmunoassays of HPLC fractions were used to demonstrate the presence of FMRFamide and FLRFamide in the heart. FMRFamide-immunoreactive (FMRFamide-IR) nerve fibers, varicosities, and neuronal somata were observed in whole-mounts of the hearts. The atrium and atrioventricular (AV) valve regions contained significantly higher densities (P < 0.05, ANOVA) of immunoreactive varicosities compared to the ventricle. The high density of FMRFamide-IR varicosities in the atrium and the lack of sensitivity of this region to FMRFamide suggest that the atrium may be a neurohemal organ for the release of FMRFamide. The presence of FMRFamide-IR somata in the Aplysia heart suggests that peripheral neurons may play a role in modifying heart activity, independent of the central nervous system.