Isolated pancreatic islets were implanted intraportally into normoglycemic or alloxan-induced diabetic C57BL/6 mice. Each animal was grafted with 200-250 syngeneic islets. Four, 8, 14, or 56 days after the transplantation, 2 to 3 x 10(5) microspheres (10 micron diam) were injected into either the portal vein or the abdominal aorta of anesthetized animals. The presence of microspheres within the islet grafts was determined in stained sections of the livers. In general, the number of microspheres in the liver sections was greater than 10 times higher in mice given microspheres via the portal route. When the microspheres were administered via the arterial system 2 wk after transplantation, approximately 20-30% of the islet sections contained microspheres; only occasional spheres were found in the islets after intraportal administration. This was the case even when as many as 56 days had elapsed. Some but not all mice investigated 4 and 8 days after transplantation had islets that contained microspheres. The intraportally implanted islets in hyperglycemic animals had decreased revascularization compared with normoglycemic mice 2 wk after implantation. The results indicate that intraportally implanted syngeneic pancreatic islets become revascularized mainly from the hepatic artery and that this process starts as early as during the 1st wk postimplantation. Furthermore, hyperglycemia seems to influence this process.