In (NZB X NZW)F1 (B/W) mice, moderate caloric intake [10 kcal (41.8 kJ) per day] from the time of weaning was associated with maintenance of lower body weight, greater capacity of spleen cells to be stimulated with T-cel mitogens, and better preserved capacity to generate cytotoxic cells in response to in vitro and in vivo stimulation with allogeneic tumor cells. Plaque-forming cell response to sheep erythrocytes was also well maintained in animals on the restricted diets when sensitization was accomplished either in vitro or in vivo.Spontaneous suppressor cell activity against plaque-forming cells that developed in controls did not appear in the mice on the restricted diet. Significantly less circulating antibody to native DNA was present in the blood of mice 10 months of age when their dietary intake had been restricted. Histological analysis revealed that the development of renal disease and the deposition of gamma globulin in the glomerular capillaries was markedly inhibited in the mice on restricted diets. Dietary restriction from the time of weaning thus appears to prolong significantly the life of autoisnmunity-prone (NZB X NZW)F1 male and female mice and to alter lymphoid cell immune function, thereby decreasing the autoimmune processes and immunological assault associated with progressive renal disease in these animals.Over the past several years, we have analyzed the influence of diet on immunologic functions in mice, rats, and guinea pigs (1). Investigations with the autoimmunity-susceptible NZB strain of mice revealed that diets relatively high in fat and low in protein and fiber accelerated development of autoimmune disease and shortened life-span. Conversely, diets high in protein and fiber and low in fat delayed development of autoimmunity and prolonged life-span (2, 3). Furthermore, chronic protein restriction with normal calorie intake from the time of weaning in NZB mice interfered with the loss of T-cell-mediated immune functions and decreased hypergammaglobulinemia, thymic involution, and splenomegaly (4). The lowprotein diets also retarded moderately the development of autoimmune disease but did not prolong life of NZB mice (4). Relatively short-term, chronic, moderate protein restriction with normal calorie intake in rats (5), mice (6), and guinea pigs (7), inhibited antibody production but permitted expression of T-cell-mediated immunity. Extreme dietary protein deficiency inhibited both production of antibody and expression of Tcell-mediated immunities. Similar influences were obtained with chronic single amino acid restrictions (8). Walford et al. (9) showed that, in long-lived strains of mice, calorie restriction early in life prolonged immunologic vigor as well as survival.We have recently reported that dietary restriction, initiated both from the time of weaning and at an adult age, prolongs significantly the life-span of short-lived, autoimmunity-prone (NZB X NZW)F1 (B/W) mice (10, 11). Dubois et al. (12)