The longevity of mice of the (NZB X NZW)Fj (B/W) strain and the DBA/2f strain of mice is dramatically prolonged by dietary restriction. B/W mice are susceptible to, and die at an early age from, immunocomplex nephritis. Mice Edelman et al. (20) found that in man protein and protein/calorie deprivation leads to deficiencies of cellular immunity attributable to deficiency in function of thymusdependent (T)-lymphocytes.Jose et al. (21) observed that although malnourished Australian aboriginal children frequently exhibited rheumatic heart disease, they rarely showed symptoms attributed in well-nourished populations to post-streptococcal rheumatic fever. Jose et al. (22) showed that antibody responses of these nutritionally deprived aboriginal children to certain antigens can be grossly deficient, whereas in vitro responses of T-lymphocytes to plant lectins are better preserved. Because analysis of the relationship of immunologic perturbations to the nutritional deficiency may be difficult under field conditions, we launched an analysis of the influence of nutrition on immune functions of experimental animals under controlled laboratory conditions. Jose et al. (23-26), Cooper et al. (27), Good et al. (28,29), and Kramer and Good (30) showed that in mice, rats, and guinea pigs moderate chronic dietary protein restriction depresses antibody production while increasing or permitting maintenance of certain cell-mediated immunities. Extreme protein deprivation produced deficiency of both cellular and humoral immunity. Profound nutritional deficiencies exerted influences from which the animals were slow to recover. In an earlier study with NZB mice we observed that breeding capacity is deficient (31). Comparisons were made, using two commercial diets that differed in proportion of animal fat and proAbbreviations: B/W, (NZB X NZW)F1 mice; calorie, the nutritionists' calorie, = 1 kcal, = 4.18 kJ, is used throughout this paper.tein. Reduction of dietary fat decreased reproductive success but prolonged life and decreased propensity to autoimmunity in NZB mice (32,33). A well-defined diet low in protein resulted in maintenance of cell-mediated and humoral immunity functions which usually decline with age in NZB mice (34)(35)(36). Autoimmune hemolytic anemia was slower to develop but was not prevented, nor was longevity increased. These studies dissociated to some degree changes in immunoglobulin levels and the declining vigor of cell-mediated immunity of NZB mice from expression of lethal autoimmune anemia. Dubois et al. (37) also noted that a low-phenylalanine and low-tyrosine diet interfered with disease expression and prolonged the life of (NZB X NZW)F1 mice.The present investigation concerns influence of different diets on longevity of short-lived, autoimmunity-susceptible mice. (NZB X NZW)F1 (B/W) mice were studied because this hybrid is short-lived due to the development of autoimmune renal disease early in life (38,39