The antinociceptive action of the gamma-aminobutyric acid (GABA) agonists THIP and baclofen was evaluated in mice using hot-plate (48 and 55 degrees C) and tail-immersion (50 degrees C) procedures. It was found that atropine reversed antinociception induced by THIP but not that induced by baclofen in the 48 degrees C test, whereas the anticholinergic drug blocked the response to both GABA agonists when the stimulus was provided by a 55 degrees C hot-plate. Atropine methylnitrate, mecamylamine, picrotoxin and bicuculline had no effect on antinociception induced by THIP or baclofen. Prior treatment with haloperidol enhanced only the response to baclofen on the 55 degrees C hot-plate. A reciprocal cross-tolerance was found between THIP and baclofen in the tail-immersion assay, although only THIP exhibited cross-tolerance to morphine. These results suggest that while the analgesic response to THIP and baclofen is partially mediated by a common system, the two agents act by independent mechanisms as well.