Theoretical studies have suggested that the output of a central pattern generator (CPG) must be matched to the properties of its peripheral effector system to ensure production of functional behavior. One way that such matching could be achieved is through coordinated central and peripheral modulation. In this study, morphological and physiological methods were used to examine the sources and actions of dopaminergic modulation in the cardiac system of the blue crab, Callinectes sapidus. Immunohistochemical localization of tyrosine hydroxylase (TH) revealed a prominent neuron in the commissural ganglion, the L-cell, that projected a large-diameter axon to the pericardial organ (PO) by an indirect and circuitous route. Within the PO, the L-cell axon gave rise to fine varicose fibers, suggesting that it releases dopamine in a neurohormonal fashion onto the heart musculature. In addition, one branch of the axon continued beyond the PO to the heart, where it innervated the anterior motor neurons and the posterior pacemaker region of the cardiac ganglion (CG). In physiological experiments, exogenous dopamine produced multiple effects on contraction and motor neuron burst parameters that corresponded to the dual central-peripheral modulation suggested by the L-cell morphology. Interestingly, parameters of the ganglionic motor output were modulated differently in the isolated CG and in a novel semi-intact system where the CG remained embedded within the heart musculature. These observations suggest a critical role of feedback from the periphery to the CG and underscore the requirement for integration of peripheral (neurohormonal) actions and direct ganglionic modulation in the regulation of this exceptionally simple system.