Using a newly developed infusion technique, the in vivo effects of forskolin and dibuturyl cyclic AMP (dbcAMP) on exocytosis and endocytosis in thyroid follicle cells were studied in thyroxine-treated rats and mice. Reactants were selectively infused via the superior thyroid artery to one thyroid lobe. The contralateral lobe served as a control. In the rat, a supramaximal i.v. dose of thyrotropin (TSH, 500 mU) induced a slight increase in thyroidal tissue levels of cyclic adenosine monophosphate (cAMP) while TSH 50 mU i.v. had no effect on cAMP levels. On the other hand both doses of TSH stimulated exocytosis, signified by a decrease in the number of exocytotic vesicles and endocytosis, signified by the appearance of pseudopods and colloid droplets. Selective thyroid infusion of dbcAMP (5 mM) or forskolin (25 microM), which induced a 10-fold increase in thyroid cAMP levels, did not induce any morphological sign of exocytosis or endocytosis in the follicle cells. The morphological response to TSH given i.v. was quantitatively unaltered by simultaneous infusion of forskolin. In contrast to the findings in rats, infusion of forskolin and dbcAMP in mice induced endocytosis. In conclusion, our findings in the mouse are in agreement with earlier studies in this and other species, indicating that cAMP mediates the effects of TSH on endocytosis and probably also on exocytosis. In contrast, our observations in the rat thyroid in vivo lead to the conclusion that cAMP is not the main intracellular mediator of exocytosis and endocytosis in this species. This conclusion is at variance with previous reports, mostly from in vitro studies.(ABSTRACT TRUNCATED AT 250 WORDS)