The immunocytochemical detection of Fos, the protein product of the immediate-early gene c-fos, was used as a marker for activated neurons to examine whether the C1 neurons in the rat rostral ventrolateral medulla (RVLM) respond to changes in baroreceptor afferent activity. After hydralazine-induced hypotension or sinoaortic denervation, two treatments that reduce baroreceptor afferent activity, numerous Fos-positive neurons were observed in the RVLM. The number of Fos-positive neurons in the RVLM was counted in brain stem sections from hydralazine-treated rats that had been previously injected with Fluorogold into the upper thoracic spinal cord to label spinally projecting RVLM neurons as well as stained for phenylethanolamine-N-methyltransferase (PNMT) as a marker of C1 neurons. The results indicate that approximately 80% of the C1 neurons expressed Fos in response to hydralazine injection; this was true of spinally projecting C1 neurons as well as those C1 neurons that were not labeled with Fluorogold. Furthermore, in hydralazine-treated rats, the majority of Fluorogold-labeled Fos-positive neurons contained PNMT. These results suggest that C1 neurons are sensitive to baroreceptor afferent input and support a role of these neurons in cardiovascular regulation.