Using a modification of the peroxidase-antiperoxidase technique, serotonin immunoreactivity was localized at the ultrastructural level in the nucleus of the solitary tract of the cat. Structures containing serotonin immunoreactivity included unmyelinated axons, varicosities (0.5 to 2 micrometers in diameter), and synaptic terminals. The serotonin-containing synaptic terminals were found less frequently than axons or varicosities. Within unmyelinated axons and varicosities, the immunoreactivity was associated mainly with large granular vesicles (80 to 150 nm). While large granular vesicles were found in all immunoreactive structures, greater numbers were observed in axons and nonsynaptic varicosities. Serial sections of several nonsynaptic serotonin-immunoreactive varicosities indicated the lack of synaptic specializations associated with these structures. In a typical section, only one or two granular vesicles were in synaptic terminals which contained numerous small clear vesicles. Serotonin-immunoreactive terminals formed asymmetrical contacts with dendrites and spines. No synaptic contacts involving immunoreactive terminals were found on cell bodies or other axonal structures. Serotonin-containing neuronal perikarya within the nucleus of the solitary tract were never observed. The abundance of nonsynaptic varicosities containing large granular vesicles suggests a possible neurohumoral role for serotonin within the feline nucleus of the solitary tract. This is discussed in relation to previous reports concerning the paucity of genuine synaptic contacts involving serotonin in other regions of the central nervous system. The presence of serotonin-immunoreactive terminals in the nucleus of the solitary tract also suggests its function as a putative neurotransmitter.