The giant neurons R3-14 in the parietovisceral ganglion of Aplysia, originally proposed to be a homogeneous group of neuroendocrine cells, are likely candidates for a multifunctional and multiple messenger status. The studies reported here suggest that individual R3-14 giant neurons not only innervate specific target tissues but appear to operate more autonomously than previously thought. Identified members of the group were traced into peripheral tissues by electrophysiological, autoradiographic, and intracellular cobalt staining techniques. Five neurons (numbered R6, R7, R8, R11, and R14) were identified on the basis of their unique patterns of axonal projections. R6 innervates the ganglionic artery and pericardial area; R7 and R8, the heart; R11, the kidney; and R14, a large number of vascular tissues. The wide distribution of R3-14 terminals innervating a variety of vascular tissues indicates that several general and local aspects of circulatory physiology are likely to be regulated by these neurons. R3-14 contain the free amino acid glycine, a putative neuromodulator that potentiates cardiac and vascular smooth muscle contraction and several small peptides of unknown, but probably neurohormonal, function. A model is proposed in which R3-14 release glycine to modulate local (e.g., hemolymph pressure and distribution) cardiovascular performance and, indirectly, metabolic homeostasis as well.