Oxytocin was administered intrathecally at a dose of 6.5 nmol to the 9th or 2nd thoracic level of the spinal cord in the rat. This increased heart rate but had no effect on arterial pressure. The increase in heart rate began within 1 and 5 min and reached a peak at 10-30 min; the maximum increase, at 10 min after administration, at the second thoracic level was 65.4 +/- 13.8 (S.E.M.) bpm (n = 9). When administration was at the 9th thoracic level the change at 10 min was 36.9 +/- 18.0 bpm (n = 14). Administration of hexamethonium systematically, to block nicotinic transmission in autonomic ganglia, prevented the cardioacceleration in response to intrathecal administration of oxytocin. When 6.5 nmol of oxytocin were administered i.v., there was an immediate decrease in heart rate by 42.5 +/- 16.5 bpm (n = 4) and an increase in systolic (6.3 +/- 6.4 mm Hg) and in diastolic (38.8 +/- 8.3 mm Hg) pressures (n = 4); this effect lasted 5-10 min. Administration of 1.625 nmol of oxytocin at the 9th thoracic level had an effect qualitatively similar to that seen with the higher dose, but the response was smaller in magnitude and more delayed in onset; 0.65 nmol of oxytocin were without effect. Transfer of label to the blood after intrathecal administration of [125I]oxytocin indicated that the level in the blood reached a maximum of 0.6% of the total injected by 30 min after administration. It is concluded that the intrathecal administration of reached a maximum of 0.6% of the total injected by 30 min after administration. It is concluded that the intrathecal administration of oxytocin increases heart rate via an action in the spinal cord, presumably on sympathetic preganglionic neurons. Our results are consistent with earlier suggestions that oxytocin may be a chemical mediator of synaptic transmission onto sympathetic preganglionic neurons.