Female sex hormones have been considered to be a risk factor for the development of cholesterol gallstone disease, because of increased cholesterol saturation of bile. Impaired gallbladder function is an additional factor which is suspect but unproved. We investigated gallbladder function in 10 young women on two occasions: first during the follicular phase of the menstrual cycle, when endogenous progesterone is low, and again after the ingestion of medroxyprogesterone acetate, 10 mg/day for 10 days, just prior to the next menstrual period. Another group, 15 young women, was studied during their luteal phase, when endogenous progesterone is high. Gallbladder filling and emptying in response to cholecystokinin (0.02 U/kg-min) was quantitated by 99mTc-HIDA cholescintigraphy. Gallbladder filling and emptying were no different in women in the follicular phase than in women in the luteal phase of the menstrual cycle. In both menstrual phases, the administration of the exogenous progestin significantly (p less than 0.05) reduced the fraction of hepatic bile entering the gallbladder. Gallbladder emptying was also depressed: the total amount ejected was less, the time to empty half the contents was prolonged, and the rate was slower (p less than 0.05). Thus, different phases of the normal menstrual cycle do not appear to have any effect on gallbladder function. Administration of an exogenous progestin, however, significantly impairs both gallbladder filling and emptying, factors which could predispose to the formation of cholesterol gallstones.