Although skin allografts from inbred donors of the Fisher strain to inbred male Lewis recipients regularly show acute rejection within 12 days, orthotopic kidney allografts between untreated animals, in this same combination of strains, usually remain functionally intact for longer than 100 days. Since such renal allografts persist despite previous or concomitant rejection of skin allografts, neither acquired tolerance nor nonspecific immunosuppression can explain the surprisingly prolonged kidney survival. Many factors appear to be responsible for the disparate survival times observed. Tentatively, these factors are (i) antigenic differences between kidney and skin, (ii) intervention of immunological enhancement, and (iii) physiological differences in vulnerability between kidney and skin.