Mice were chronically treated with morphine or ethylketocyclazocine in order to induce a marked tolerance to their antinociceptive effect in the phenyl-p-benzoquinone writhing test. TRH (2 mg kg-1 i.p.) significantly reduced the number of writhes in non-tolerant mice, but did not alter the response of morphine- or ethylketocyclazocine-tolerant mice. TRH did not modify the binding of [3H]naloxone in mouse brain either in vitro (TRH: 10(-10)-10(-4) M) or ex vivo (TRH: 1-40 mg kg-1 i.p.). There was no dose-dependent modification of the in vivo binding of [3H]lofentanil in any of the mouse brain areas studied after TRH (1-40 mg kg-1 i.p.).