A growing body of evidence suggests that thyrotropin-releasing hormone (TRH), and endogenous brain tripeptide, produces behavioral excitation in a variety of mammalian species. This study evaluated the cardiopulmonary and antidepressant response to a single intravenous (i.v.) bolus of TRH in sodium pentobarbital (33 mg.kg-1) anesthetized dogs. TRH (0.5 and 1 mg) produced a significant dose-dependent decrease in sleeping time (33% and 51%, respectively) when compared to i.v. vehicle (1 ml of 0.9% NaCl)-treated animals. Of interest was the finding that the high (1 mg), but not the low (0.5 mg) dose of TRH significantly (P less than 0.01) increased mean arterial pressure and heat rate. In addition, i.v. TRH (1 mg) significantly (P less than 0.01) decreased tidal volume. A trend toward increased respiratory frequency in TRH-treated dogs was noted, this difference, however, did not reach statistical significance. In conclusion, the results of this study support the view that TRH, and endogenous brain hormone, may have an important clinical application in cases where stimulation of the central nervous system is required.