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, Rll, 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; Rll, 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.Many invertebrate neurons can be identified by their size, color, and location within the nervous system, as well as by their endogenous spike activity and synaptic input. In the parietovisceral ganglion (PVG) of the mollusc Aplysia, for example, perhaps 5% of its neurons in the PVG have been used for singlecell level studies on the neural organization underlying defined behavior, learning, neurochemistry, and expression of genetic information. The functions of many of the other PVG cells are not known because it has been difficult, in many cases, to trace peripheral axons. Intracellular stains often travel only short distances in these large neurons (Winlow and Kandel, 1976) and electrophysiological tracing can be a tedious task with low return. These factors have limited study of the most distinctive group of giant cells in Aplysia, the 12 "white cells" (numbered R3-14) in the PVG, neurons whose peptide synthesis, endogenous electrical activity, and general morphology have been described, but whose function(s) are largely unknown (Coggeshall, 1967;Coggeshall et al., 1966;Frazier et al