Previous studies have demonstrated that underfeeding in both premature and young mature animals may extend the life span as well as preserve the functions of the immune system. The effects of caloric restriction for a period of 12 months on different organs as well as the formation of brain-reactive antibodies in young mature mice (3 months) were tested. These animals showed a significantly lower weight of the total body and various organs including the brain, spleen, adrenals and kidneys. The brain weight/body weight ratio, on the other hand, was significantly higher in these mice. Sera in the dietary animals were mostly negative while those of control animals of the same age and sex had high levels. The present study supports the earlier observations that controlled dietary restriction is able to slow down the age-related deterioration of the immune system. The inhibition of brain-reactive antibody formation in these animals might also be related to a delayed onset of autoimmune disorders.