TRH was shown to be an extremely potent (ED50 = 0.04 mg/kg, IP) antagonist of isolation-induced aggression in male mice. The antifighting activity of TRH was selective in that it did not produce concurrent neurological impairment or significant alterations in spontaneous locomotor activity at antiaggressive doses. This activity of TRH appeared to be a direct affect on CNS structures since neither triiodothyronine nor any of the constituent amino acids of TRH antagonized aggression in isolated mice. The results are discussed in terms of the recent clinical effectiveness of TRH in some cases of mental illness (e.g., depression and schizophrenia).