We studied the effects of the oral administration of a stable prostaglandin E2 analog, 16,16-dimethyl prostaglandin E2, on the intrahepatic biliary branches in a canine model. Obstructive cholestasis with a bacterial infection was induced surgically in two liver lobes in healthy mongrel dogs, and 16,16-dimethyl prostaglandin E2 was administered orally. We examined the morphological changes in the intrahepatic biliary branches and quantitatively estimated density of mucus-producing glandular elements in the ductal wall by counting these glands per unit area. Dogs treated with 16,16-dimethyl prostaglandin E2 (group 1) demonstrated fibrous thickening of the ductal wall, moderate infiltration by inflammatory cells and severe adenomatous hyperplasia of the bile duct epithelium, including striking proliferation of the mucous glands. The mean number of these mucous glands per unit area (4 mm2) was 43.0 ± 9.0 (mean ± S.D.; range = 36 to 56). In contrast, in a control group whose members did not receive 16,16-dimethyl prostaglandin E2 (group 2), the mean number of mucous glands per unit area was 19.4 ± 8.0 (range = 10 to 29), significantly lower than that in group 1, although histological examination revealed chronic inflammation in the region of the large bile duct similar to that in group 1. These findings suggest that the increase in the number of mucous glands that typically occur in the setting of bile stasis and biliary infection is enhanced by 16,16-dimethyl prostaglandin E2. (HEPATOLOGY 1993;17:1062–1065.)