When applied in vitro to various CNS structures 5-HT and/or NMDA have been observed to generate rhythmic nervous activity. In contrast, reports of similar in vivo actions are relatively rare. Here we describe a physiological sympathetic motor rhythm regulating the thermoregulatory circulation of the rat tail (T-rhythm; 0.40-1.20 Hz) that can be elicited following intrathecal (i.t.) application of 5-HT to an in situ'isolated' spinal cord preparation (anaesthetized rats spinalized at T10-T11 and cauda equina cut). i.t. injections were delivered to L1 as sympathetic neuronal activity to the tail (SNAT) arises from preganglionic neurones at T11-L2. SNAT was abolished after spinal transection (n = 18) and it did not return spontaneously. The administration of 5-HT (250 nmol) generated rhythmic sympathetic discharges (n = 6). The mean frequency of the T-like rhythm during the highest level of activity was 0.88 +/- 0.04 Hz which was not significantly different from the T-rhythm frequency observed in intact animals (0.77 +/- 0.02 Hz; P > 0.05 n = 16). In contrast, NMDA (1 micromol) generated an irregular tonic activity, but it failed to generate a T-like rhythm (n = 9), even though the mean levels of activity were not significantly different to those produced by 5-HT. However, 5-HT (250 nmol) applied after NMDA generated a T-like rhythm (0.95 +/- 0.11 Hz, n = 6). Our observations support the idea that 5-HT released from rostral ventromedial medullary neurones, known to innervate sympathetic preganglionic neurones, can induce sympathetic rhythmic activity.