Activation of nociceptive somatic afferents excites hypothalamic neurosecretory cells and stimulates the release of vasopressin. To investigate the possibility that relevant afferent information is relayed through the A1 norepinephrine cell group of the caudal ventrolateral medulla, single-unit recording experiments were performed in pentobarbital sodium-anesthetized rats. The effects of somatic nerve stimulation, application of noxious somatic stimuli, and A1 region stimulation on the activity of putative vasopressin-secreting neurosecretory cells of the supraoptic nucleus were compared. The predominant effect of femoral and sciatic nerve stimulation on these cells was excitation, 54% (n tested = 113) displaying a marked increase in discharge probability, which had a mean onset latency of 72 +/- 3 ms and a mean duration of 114 +/- 9 ms. Almost all cells (96%) responding to somatic nerve stimulation were also excited by pinching of the ipsilateral or contralateral hindlimb paw, and the majority (84%) displayed a matching but shorter latency response to A1 region stimulation (mean onset 35 +/- 4 ms, duration 55 +/- 9 ms). A1 region injections of the inhibitory neurotransmitter gamma-aminobutyric acid reversibly blocked the effects of both somatic nerve stimulation (n = 14) and paw pinch (n = 9) on putative vasopressin cells. These results indicate that excitation of vasopressinergic neurosecretory cells by noxious somatic stimuli requires activation of neurons of the caudal ventrolateral medulla and hence are consistent with the proposal of a role for the A1 norepinephrine cell group.