The aim of this study was to explore the effects of nutritional manipulations on the occurrence and progression of age-related pathologic lesions in male Fischer 344 rats. The following nutritional regimens were studied: (a) ad libitum feeding, (b) food restriction initiated at 6 weeks of age, (c) food restriction initiated at 6 months of age, (d) food restriction limited to a period of early life (6 weeks to 6 months of age), (e) protein restriction without caloric restriction. The major age-related lesions observed were chronic nephropathy, cardiomyopathy, and neoplasia. Food restriction initiated at 6 months of age was as effective as food restriction initiated at 6 weeks of age in slowing the progression of chronic nephropathy and cardiomyopathy and in delaying the occurrence of neoplasia. Food restriction limited to early life was much less effective. Protein restriction in the absence of caloric restriction did not delay the occurrence of neoplasia, but it did retard chronic nephropathy and cardiomyopathy, although much less effectively than caloric restriction involving a similar level of protein restriction.