Cytosolic receptors for estrogen and progesterone were assayed in 50 gallbladders from 29 women and 21 men who had cholecystectomies because of cholelithiasis. High-affinity (equilibrium dissociation constant, KD = 0.46 +/- 0.23 nmol/L of 24 cases) estrogen receptors were detected in 20 of 29 gallbladders from women (range = 1.6 to 32 fmol/mg protein; mean +/- S.D. = 10.9 +/- 8.1), whereas in men only 4 of 21 specimens contained detectable estrogen receptors. High-affinity (KD = 0.45 +/- 0.17 nmol/L; mean +/- S.D. of 41 cases) progesterone receptors were found in 25 of 29 gallbladders of women (range = 2 to 62 fmol/mg protein; mean +/- S.D. = 19.2 +/- 14.4) and in 16 of 21 gallbladders of men (range = 4 to 36 fmol/mg protein; mean +/- S.D. = 12.5 +/- 8.5). There is a statistically significant difference between men and women in the proportion of estrogen receptor-positive gallbladders, 19% and 69% for men and women, respectively. Progesterone receptors are present in similar proportion in the gallbladders of men (72.2%) and women (86.2%). In women a positive correlation between estrogen and progesterone receptors was found. Even in the absence of estrogen receptors, the gallbladders of men express progesterone receptors at levels similar to those observed in women. At least in cholelithiasic gallbladders, this suggests that a sex difference exists in the coexpression of estrogen and progesterone receptors. Such a difference could be related with the higher gallstone incidence in women than in men.