Wholemount immunohistochemical methods were used to examine the localization of gamma-aminobutyric acid (GABA) and glutamate within the cardiac system of the Caribbean spiny lobster Panulirus argus. All of the GABA-like immunoreactivity (GABAi) in the cardiac ganglion originated from a single bilateral pair of fibers that entered the heart via the two dorsal nerves. Each GABAi axon bifurcated upon entering the ganglion and gave rise to varicose fibers that surrounded the somata and initial segments of the five large motor neurons. The four small posterior cells did not appear to receive somatic contacts. Double-labeling experiments in which individual motor neurons were injected with Neurobiotin showed that their dendritic processes, which project to muscle bundles adjacent to the ganglion and are thought to respond to stretch, were also accompanied by branches of the GABAi fibers. Glutamate-like immunoreactivity (GLUi) was present in each of the motor neuron cell bodies. In some preparations, GLUi was also detected in large caliber fibers in the major ganglionic nerves. These fibers gave rise to more slender branches that innervated the cardiac muscle bundles. GLUi was also found in the small cell bodies and in fibers surrounding motor neuron somata. Taken together, these findings support previous electrophysiological, pharmacological and anatomical studies indicating that GABA mediates extrinsic inhibition and that glutamate acts as a neuromuscular and intraganglionic transmitter in this system. While axosomatic contacts may play a major role in both transmitter systems, the GABAergic inhibition also appears to involve substantial axodendritic synaptic signaling.