The present study was done to establish whether peptidergic afferent inputs can modulate parasympathetic neurons of the guinea-pig cardiac ganglion. Whole mount preparations from the guinea-pig heart were utilized to localize afferent terminals by immunohistochemistry and for intracellular recordings from individual neurons in situ. Action potentials could be elicited by both intracellular current injection and stimulation of interganglionic fiber bundles. Two types of neuron, phasic (95%) and tonic (5%) as defined by their firing properties, were observed. High frequency (5-10 Hz) interganglionic fiber stimulation produced a calcium-dependent, slow depolarization in many cells which was not blocked by 100 microM hexamethonium or 1 microM atropine. A prolonged depolarization was also produced by local application of capsaicin (1 mM), which releases substance P and CGRP from afferent nerve terminals. Microinjection of the mammalian tachykinins substance P, neurokinin A and neurokinin B (all at 100 microM), also produced a slow depolarization. Application of specific agonists for the tachykinin receptor subtypes indicated that these neurons express both NK2 and NK3 receptors. Individual cells were filled with neurobiotin to examine their morphology and the preparations were counter-stained for SP-like immunoreactivity. The results demonstrated that SP-positive fibers are found in close apposition to both phasic and tonic neurons. From these results, we suggest that the parasympathetic neurons of the guinea-pig cardiac ganglion receive inputs from peptidergic, afferent fibers and that this input provides a pathway for potential local reflex control of cardiac function.