The influence of hypophysectomy on biochemical indices of striatal dopamine target cell supersensitivity induced by prolonged haloperidol treatment was investigated in the rat. Hypophysectomy itself did not modify dihydroxyphenylacetic acid (DOPAC) levels but slightly enhanced acetylcholine concentrations in the striatum. Hypophysectomy failed to affect the ability of haloperidol, apomorphine and pergolide to alter these biochemical parameters after acute administration. Prolonged administration of haloperidol (by means of osmotic minipumps delivering 2.5 micrograms/h) for 14 days caused a decrease in DOPAC and an increase in acetylcholine levels in the striatum during withdrawal; these effects were of a similar magnitude in sham-operated and hypophysectomized rats. Moreover, there was a similar degree of tolerance to the elevation of DOPAC and to the diminution of acetylcholine concentrations in striatum in response to challenge with haloperidol during withdrawal in sham-operated and hypophysectomized animals. Finally, a similar supersensitive biochemical response to pergolide (decrease in DOPAC and increase in acetylcholine levels) was observed in both hypophysectomized and sham-operated animals after prolonged haloperidol treatment. These data suggest that hypophyseal factors do not affect the development of striatal dopamine target cell supersensitivity caused by prolonged haloperidol treatment.