Thyrotropin-releasing hormone (TRH) and a structurally related analogue of TRH, MK-771, administered IP or orally, restored flex or reflex activity in rats with acute spinal transections. The effect of MK-771 in this test was not modified by pretreatment with reserpine plus alpha-methyl-p-tyrosine but was antagonized by the alpha-adrenergic blocking agent, phenoxybenzamine. However, another alpha-adrenergic blocking agent, HEAT, was ineffective in this regard. Additionally, TRH and MK-771 restored the anticonvulsant actions of methazolamide in mice pretreated with reserpine or picolinic acid. These data, along with the findings that MK-771 and TRH enhance depletion of brain norepinephrine induced by alpha-methyl-p-tyrosine, indicate that these agents may affect central noradrenergic mechanisms. Whether the mechanism of their proposed effect upon noradrenergic systems is direct or mediated by an interaction with another neurotransmitter system which influences noradrenergic function cannot be determined on the basis of the present studies.