The effect of ethanol [1 g/kg per orally (p.o.) during 1 hr] after thyrotropin-releasing hormone (TRH) pretreatment (five doses of 20 mg p.o. during 30 hr preceding ethanol intake) was studied in a placebo-controlled, double-blind design in 11 healthy subjects. Computerized reaction tests measuring errors and reaction time, as well as clinical testing and a self evaluation (modified Osgood test) were performed before, 75, 150, and 225 min after ethanol intake. TRH treatment did not influence blood ethanol concentrations. The effect of ethanol to produce errors was substantially reduced in all three reaction tests after TRH treatment compared to placebo treatment. The reaction times were slightly increased in simple and four choice reaction tests and up to 20% increased in a complex test in the TRH-ethanol situation compared to the placebo-ethanol situation. The effects caused by ethanol were also significantly reduced in three clinical tests and in two subjective tests of inebriation by TRH treatment compared to placebo treatment. In conclusion the study demonstrated that several acute effects of ethanol intake in humans were reduced by TRH pretreatment which did not interfere with the blood ethanol concentration versus time curve.