BACKGROUND: Transplanted metanephroi vascularize and develop features of mature kidney. One group reported the intriguing finding that metanephric allografts and congenic, major histocompatibility complex-mismatched grafts developed without rejection in the absence of immunosuppression. Our experiments aim to investigate the hypothesis that metanephroi lack immunogenicity and identify immunosuppressives that do not inhibit development. METHODS: We transplanted syngeneic metanephric grafts, allografts, and class II mismatched transplants to adult rats along with control grafts to nude recipients. glomerular filtration rates (GFRs) were measured where possible and transplants assessed by histology, immunohistochemistry, electron microscopy, and polymerase chain reaction. RESULTS: Allografts underwent reliable growth and vascularization followed by vigorous rejection (n>200). Rejection was conserved across a class II-mismatched strain and when the earliest dissectable metanephric structures were transplanted. Immunosuppressive drugs other than cyclosporine demonstrated no in vivo toxicity to transplants and treatment with FTY720 and tacrolimus could ablate histologic evidence of allograft rejection. Syngeneic transplants exhibited function of up to 8% of a normal GFR. Renal mass reduction and growth factor treatment was associated with higher GFR than controls. The anatomical site of implantation was also linked strongly with achieved function. CONCLUSIONS: Fetal kidney rudiments can provide a source of functioning renal tissue. These results suggest that such structures are no less immunogenic than mature organs, but the observed rejection is controllable.