A light and electron microscopic study has been made of the substance P-immunoreactive networks formed by sensory nerve fibres in the prevertebral sympathetic ganglia of the guinea pig to seek confirmation that these networks arise from collateral branches of sensory fibres passing through the ganglia and to explore the synaptic and other specialized relationships established by these networks. Slices from coeliac-superior mesenteric and inferior mesenteric ganglia of young adult males, perfusion-fixed by paraformaldehyde, were immunostained with a monoclonal antibody to substance P, and the immunolabelling was visualized by a peroxidase reaction. Immunolabelled fibres passing through the ganglia were seen by light microscopy to give off varicose collaterals that ramified in the ganglionic neuropil. Electron microscopy showed that the parent fibres were almost exclusively unmyelinated. Many collaterals ran directly beneath the basal lamina bordering the intraganglionic tissue spaces, and the varicosities either remained superficially exposed under the basal lamina or sank deeper into the supporting Schwann cells, becoming apposed to dendrites of the ganglionic neurones, upon which they formed synapses, or to other nerve terminals. The incidence of these specific associations was quantified, singly and in combination. Synapses could be situated at the same level as unlabelled synapses on the same dendrite, and exposed varicosities could lie within 0.5 micron of exposed, postsynaptic dendrites. These observations confirm a collateral, synaptic nature for the networks and suggest additional nonsynaptic modes of release and sites of transmitter action. They are consistent with the hypothesis that the system serves a nocifensor function of axon reflex type.