It is frequently stated that high fat diets are harmful with respect to nutrition and disease development. Herein, (NZB/NZW)F1 autoimmune-prone mice were compared under the influence of different calorie intakes and different calorie sources. Decreased calorie intake prolonged life and delayed onset of glomerulonephritis. This influence of restriction of energy intake was greater than any influences of dietary energy source. Parameters affected strictly by restricted calorie intake were: 1) longevity, 2) delayed onset of glomerulonephritis, 3) greatly decreased circulating immune complexes, 4) decreased production of anti-DNA antibodies, 5) increased thymocyte proliferation in response to exogenous Interleukin-2 (IL-2), 6) increased IL-2 production by spleen cells stimulated by concanavalin A and 7) marked increase of mixed lymphocyte reaction of spleen cells. Parameters affected both by restriction of calorie intake and by high sucrose content in full-fed mice and not obviously related to longevity and protection from glomerulonephritis were: 1) plaque-forming cell response to sheep red blood cells in vitro and 2) cytotoxic cell-mediated immune response generated by in vitro exposure to allogenic antigen.