The effects of age and dietary restriction on immune response were investigated using an animal model of accelerated senescence (senescence accelerated mouse, SAM). The experimental groups consisted of control (ad libitum fed) and restricted groups (fed 60% of energy intake of the controls). Spleen weight and total number of splenic cells were significantly lower in the food-restricted group at 8 mo of age. Percentages of T (Thy-1.1+) and B (surface Ig+) cells in the splenic cells were not significantly different between the two groups. The number of direct hemolytic plaque-forming cells per 10(6) spleen cells 4 d following immunization with sheep red blood cells and dinitrophenyl-Ficoll was significantly greater in the 8-mo-old mice in the food-restricted group than in the control group. In the latter group, antibody responses Progressively decreased with age. Mitogen responses to concanavalin A and lipopolysaccharide were maintained in the food-restricted group but were depressed in the control group at 8 mo. In addition, though autoantibody to single-stranded DNA increased in the control group with advancing age, there was a steady decrease in the food-restricted group until 8 mo. Serum immunoglobulin (IgA and IgM) concentrations were significantly lower in the food-restricted group than in controls at 8 mo of age. Therefore, our results suggest that when senescence accelerated mice are subjected to food restriction, there may be a modulatory effect on the immune dysfunction associated with advancing age.