Previous studies from our laboratory have shown that stimulation of the brainstem in the area of the descending lateral serotonin containing neurons of the B3 group in the rostral ventrolateral medulla (RVLM), increases blood pressure and serotonin release in the spinal cord. The present experiments were designed to investigate the spinal cord serotonin receptor subtypes involved in mediating this pressor response. The area of the B3 neurons in the RVLM was electrically stimulated and the effects of intrathecally administered methysergide, an antagonist of 5HT1 and 5HT2 receptors, of ketanserin, a 5HT2 receptor antagonist or of ICS 205930 (ICS) or MDL 72222 (MDL), antagonists of 5HT3 receptors, were examined. Electrical stimulation of the area of the B3 serotonin-containing neurons in the RVLM increased mean arterial pressure. Intrathecal methysergide treatment attenuated the pressor response, but intrathecal MDL, ICS, ketanserin or saline were without effect. These results suggest that the pressor responses seen after stimulation of the area of the B3 serotonin neurons in the RVLM may be mediated through activation of spinal 5HT1 receptors.