The responses of pontomedullary raphe neurons to electrical stimulation of the medullary reticular formation (MRF) and the mesencephalic ventral periaqueductal gray region (PAG) were studied using intracellular methods in chloralose-anesthetized cats. Single shock stimulation of PAG at the level of the trochelear nucleus evoked short latency, monosynaptic excitatory postsynaptic potentials (EPSPs) in antidromically identified raphe-spinal neurons. Similar large EPSPs were produced by medullary reticular stimulation of either side. The large majority of raphe-spinal neurons responded to sciatic nerve shock, and most responded to tooth pulp or forepaw shock as well; these responses were always bilateral. The responses of cells that could not be antidromically invaded from spinal cord were similar to those of raphe-spinal neurons, but tended to be more variable. Intracellular injection of horseradish peroxidase into electrophysiologically characterized cells revealed that most recordings were made from large and medium sized raphe neurons. These findings are discussed in the context of a potential role for pontomedullary raphe neurons in nociception.