Glycoprotein hormone and/or subunit secretion has been increasingly recognized in patients with pituitary nonsecretory adenomas and alpha-subunit secretion has been reported to occur in 5-10% of all pituitary tumors. We investigated the dopaminergic regulation of alpha-subunit secretion in four patients with alpha-subunit secreting pituitary adenomas documented by serum and immunocytochemical studies. In three of the four patients there was a significant decrease in serum alpha-subunit concentrations during 6 weeks of bromocriptine administration. Tumor size decreased in two patients. In pituitary tumor cells from one patient cultured in vitro, dopamine caused a highly significant decrease in media alpha-subunit concentrations. To investigate whether dopaminergic regulation of alpha-subunit secretion occurs at a pre- or posttranslational level, messenger RNA (mRNA) from cultured tumor cells from one patient was analyzed by Northern blot techniques. A decrease in alpha-subunit mRNA occurred in cells incubated with 10(-10), 10(-8), and 10(-6) M dopamine. We conclude that dopamine suppressed pituitary tumor alpha-subunit secretion and mRNA levels. Dopamine agonists may be of benefit in the therapy of patients with such tumors.