The effect of cysteamine, a specific somatostatin depletor, on biliary secretion was studied in urethane-anesthetized rats. Different groups of rats received ip cysteamine at 25, 100 or 340 mg/kg just before bile collection commenced. Other groups of rats were pretreated with cysteamine (340 mg/kg ip) at 4 or 24 h prior to bile duct cannulation and bile collection. Bile secretions were collected at 30-min intervals for 4 h after bile duct cannulation. Total proteins, cholesterol, total lipids, glucose and several hepatic enzymes were assessed in bile. Results indicated that basal bile secretion was only slightly reduced and tended to decrease after drug administration (13% decrease after 340 mg/kg). Cysteamine induced dose-dependent decrease in protein secretion, and the maximum effect was reached at a dose of 340 mg/kg. The effect of cysteamine on protein secretion was prolonged, since it was still observed 24 h after the treatment with cysteamine. Cholesterol and lipid secretion was inhibited by 52.5 and 42.5%, respectively, by the drug, with the latter effect being evident 24 h after drug administration. In addition, the drug inhibited biliary glucose and aspartate aminotransferase concentrations, but increased that of alkaline phosphatase. The results suggest that acute administration of cysteamine inhibits protein, cholesterol and lipid secretion into bile.