The ability of porcine islet-like cell clusters (ICC) to cure diabetic nude rats after transplantation (tx) into one of three different implantation sites was investigated. Streptozotocin-diabetic (50 mg/kg BW) nude Rowlett rats were transplanted with 40 microliters of packed ICC (approximately 4500 ICC) either under the kidney capsule, intraportally, or into the spleen. After transplantation the rats were treated with insulin every second day; insulin therapy was discontinued four days before blood glucose determinations (6, 8, 12 and 16 wk after tx) or when graft function was obtained. Six weeks after tx all rats implanted under the kidney capsule (n = 13) had blood glucose concentrations which were significantly lower than before transplantation. However, six of these rats slowly returned to hyperglycemia, whereas seven rats remained normoglycemic with normal intraperitoneal glucose tolerance tests. The return of hyperglycemia seen in some of the rats transplanted under the kidney capsule may be due to rejection, since older nude rats may show a development of T lymphocytes. After nephrectomy in four of these rats, all reverted to hyperglycemia. The rats transplanted intraportally (n = 9) or into the spleen (n = 6) remained hyperglycemic throughout the study (16 wk). It is concluded that porcine islet-like cell clusters cure diabetic nude rats when transplanted under the kidney capsule, but not when implanted into the liver or spleen.