The effect of TRH on pentobarbital narcosis in 21 rhesus monkeys was examined. Vital signs monitored included respiration rate, heart rate, temperature, sleeping time,and time of reappearance of certain reflexes. Blood samples were obtained for pentobarbital assay. Two dose schedules for TRH administration were used. One group of 6 animals received a single dose of 20 mg/kg 30 min after barbiturate administration, while the other group were received 3 injections of 20 mg/kg spaced at 30, 40 and 50 min after injection of pentobarbital. Both groups were sex balanced. TRH administration resulted in dramatically increased respiration and heart rates and arrested the progress of barbiturate induced hypothermia. The extended dose schedule prolonged increased respiration rate and a differential effect of TRH on pentobarbital induced hypothermia across sexes was observed. All animals regained reflexes sooner and sleeping time was reduced by 22%. No differences in pentobarbital blood levels with TRH were observed. These results extend earlier work in rodents to primates and suggest a possible use of TRH in cases of acute barbiturate intoxication.