Besides its potent immunosuppressive properties, rapamycin also has antitumor and antifungal effects. Rapamycin also inhibits the proliferation of fibroblasts and therefore may impair the healing of various tissues. We investigated the effect of rapamycin on the healing of the bile duct anastomosis. The study was undertaken in pigs that were subjected to a laparotomy under general anesthesia. The bile duct was mobilized and divided and immediately reanastomosed. The animals were randomly allocated to receive either rapamycin or placebo. The animals were sacrificed on the postoperative day 5, then the biliary anastomosis was excised and used to determine the tensile strength, hydroxyproline levels, and the histological changes. The tensile strength and the hydroxyproline levels in the biliary anastomosis were lower in the animals treated with rapamycin. The liver function tests were normal. These studies show that rapamycin may impair the healing of the biliary anastomosis.