Many different theoretical approaches may be taken toward understanding the association between aging and immunologic malfunction. The leading theory is based on the natural phenomenon of thymic involution and argues that the T-dependent lymphoid system is genetically programmed to decline in effectiveness, possibly through altered endocrine and central nervous system controls. The "thymic time clock" theory of aging is strongly supported by the consistent finding of defective cellular immunity functions in aged humans and animals and an associated development of the age-related diseases. In several animal models, including autoimmune-prone strains, high spontaneous tumor incidence strains, and normal long-lived strains, it has been possible to forestall the development of the major diseases of aging and extend longevity by restricting diet. The predominant effect of dietary restriction is prolongation of immunologic vigor and retardation of the immunologic dysfunction that normally occurs with age. Studies on environmental factors affecting longevity such as these and others which demonstrate a complex interaction between genes influencing longevity underscore the complexity and challenge of aging research.