The protooncogene c-fos is expressed rapidly, transiently and polysynaptically within neurons in response to synaptic activation and voltage-gated calcium entry into the cell. The nuclear protein product of this gene (Fos) is detectable immunohistochemically 20-90 min after cell activation and remains within the nucleus for hours after expression. The present study was undertaken to identify cells within the rat medulla oblongata that express Fos-like protein in response to stimulation of afferent fibers of the carotid sinus nerve (CSN). Direct electrical stimulation of the CSN in anesthetized animals or hypoxic stimulation in either anesthetized or awake animals resulted in a consistent and discrete distribution of Fos-like immunoreactivity (Fos-LI). Fos-LI was observed bilaterally within nucleus tractus solitarius (NTS) and the ventrolateral medulla (VLM), within area postrema and nucleus raphe pallidus, and bilaterally along the ventral medullary surface. Unstimulated animals were devoid of Fos-LI within the medulla oblongata. Furthermore, neither the surgical preparations alone nor the effects of anesthesia could account for the extent of Fos-LI observed. We believe these cells represent second- and higher-order neurons within the baroreceptor and chemoreceptor reflex pathways.