To ascertain the central mechanism of the effects of thyrotropin-releasing hormone (TRH) on the cardiovascular system, we evaluated the effects of this neuropeptide on unit fires in the rostral ventro-lateral medulla (RVL), mean arterial pressure (MAP), and heart rate (HR) in normotensive and hypotensive rats. Intracerebroventricular injection (i.c.v.) of 10 micrograms TRH significantly increased MAP and HR in both normotensive and hypotensive rats. No similar effects were observed after saline injection. If electrolytic lesions of bilateral RVL were made, the cardiovascular effects of TRH i.c.v. failed to occur. TRH i.c.v. markedly increased the firing frequency of most units in the RVL. In particular, TRH i.c.v. increased the firing frequency of most units excitatory to a fall in MAP and decreased the firing frequency of most units inhibitory to a fall in MAP in normotensive rats. Moreover, a drop of MAP as low as 40 mmHg for 10 min resulted in an increase of the firing frequency of most units. The effect of TRH i.c.v. on the RVL units in the hypotensive rats was similar to that in the normotensive rats. Our findings suggest that TRH is able to intensify the cardiovascular activities and the RVL plays a key role in the effects of TRH on the cardiovascular system in both normotensive and hypotensive rats.