The purpose of this study was to determine whether enterocyte transplantation could be used to correct a specific genetic metabolic defect. Bilirubin uridine diphosphoglucuronyl transferase (UDPGT) activity has been demonstrated in normal rat intestinal mucosa. We hypothesized that normal rat enterocyte transplantation may restore the ability of Gunn rats, which lack bilirubin UDPGT, to conjugate bilirubin. Small intestine was resected from normal Wistar rat donors. Enterocytes were harvested and suspended in Dulbecco's modified Eagle's medium with 10 percent fetal calf serum. Isolated enterocytes were attached to collagen-coated dextran microcarriers and transplanted into congeneic Gunn rat recipients. Recipient rats underwent bile duct cannulation after transplantation, and bile was analyzed for bilirubin glucuronides by high-pressure liquid chromatography. Fifty percent of the transplanted rats showed a significant increase in the concentration of bilirubin monoglucuronide and diglucuronide in their bile 4 and 7 days posttransplantation. Recipient rats had well vascularized microcarrier-enterocyte aggregates in the peritoneal cavity. Our method for intraperitoneal transplantation of isolated enterocytes in rats could potentially be used to correct specific enzymatic and metabolic defects.