The ideal site to transplant pancreatic islets has yet to be determined. To evaluate this problem, we have compared the efficacy of pancreatic microfragments transplanted into the splenic, intrahepatic and renal subcapsular sites. Function was assessed by plasma glucose (PG) and intravenous glucose tolerance test (ivGTT). Portal pressures and coagulation profiles (PT, PTT, FDP, Platelet count) were measured following intrasplenic and intraportal transplants. Liver enzymes (LDH, Alk. Phos., SGOT), serum bilirubin, BUN and creatinine were assessed serially in all groups. Nine of 10 dogs that received islets refluxed into the spleen were normoglycemic (mean PG = 94.5 mg/dL) at 1 mo with one dog failing four days following implantation (PG = 350 mg/dL). Following intraportal embolization, two of six dogs remained normoglycemic (PG = 95.7 mg/dL) at 1 mo. One dog died due to mesenteric venous thrombosis, two died suddenly within 24 h of engraftment without obvious cause, and a fourth died six days following transplantation (PG = 678 mg/dL). None of the six renal subcapsular transplants induced normoglycemia (mean PG = 430 mg/dL) at 1 mo. Mean rise in portal pressure (cmH2O +/- SEM) during intrasplenic and intraportal transplantation of islets was 1.7 +/- 0.6 and 31.2 +/- 3.3 respectively (p less than 0.001). Following intrasplenic and intrahepatic engraftment, significant coagulation abnormalities did not occur. Elevation of liver enzymes occurred 24 h following implantation to all three recipient sites but returned to preoperative values by 1 mo. Bilirubin was not affected. Renal function tests were not significantly altered in any groups.(ABSTRACT TRUNCATED AT 250 WORDS)