Xenotransplantation of pig islets under the kidney capsule (KC) of diabetic rats was performed. Natural preformed ACI rat anti-pig leukocytotoxicity, leukoagglutination and hemagglutination antibody titers ranged from Neat-1: 16, 1:8-1:32 and 1:128-1:256, respectively (n = 14). Normal ACI sera were non-toxic to pig islets during short term incubation. Pig islet xenograft survival times in the nonimmunosuppressed ACI rats, ACI rats immunosuppressed with antithymocyte serum (ATS) or cyclosporin A were 3.8 +/- 0.4 (mean +/- SE; n = 5), 10.4 +/- 0.7 (n = 13) and 6.0 +/- 1.0 (n = 5) days, respectively. Pig islets implanted in the abdominal testis of ACI recipients immunosuppressed with 5 doses ATS survived for a mean of 6.4 +/- 1.0 days (n = 7). The mean K rate following an intravenous glucose tolerance test (IVGTT) in ACI rats 1 week after transplantation with pig islet under the KC was 2.2 +/- 0.4 (n = 10) compared to that of 2.91 +/- 0.30 found in normal control rats (n = 8). Peak insulin at 1 min was 60.1 +/- 3.9 microU/ml (n = 4). Histological and immunohistochemical examination showed that the xenograft from recipients treated with 5 doses of ATS still contained well-preserved islet tissue with many insulin- and glucagon-containing cells on the day of graft removal when blood glucose had returned to hyperglycemic level. Both CD4 and CD8 positive cells were in the vicinity of the graft tissue.(ABSTRACT TRUNCATED AT 250 WORDS)