Studies were carried out to explore the influence of soy protein and food restriction on age-related changes in serum PTH and bone. Three groups of male Fischer 344 rats were studied from 6 weeks of age. Group A rats were fed ad libitum diet A, which has casein as the protein source. Group B rats were fed diet B (with casein as protein source) at 60% of the mean ad libitum food intake. Group C rats were fed ad libitum diet C, which has soy protein as the protein source. The animals were killed at periodic intervals beginning at 6 months of age after an overnight fast. Serum PTH, measured with an intact N-terminal-specific RIA, and immunoreactive calcitonin increased progressively with aging. The increase was markedly suppressed by food restriction, and in the case of PTH by the soy protein diet as well. Serum creatinine started to increase after 18 months of age, and both dietary regimens of groups 2 and 3 retarded the increase. Aging was associated with a fall in serum 25-hydroxyvitamin D, and loss of bone occurred during the terminal part of life in the ad libitum-fed animals. These were prevented by food restriction, while the soy protein diet delayed the onset of bone loss. We conclude from these findings and other data from this study that in the male F344 rats 1) an age-related increase in serum PTH precedes an age-related increase in serum creatinine concentration; 2) an age-related decline in renal function probably contributes to age-related hyperparathyroidism, which, in turn, contributes to senile bone loss; 3) food restriction inhibits age-related hyperparathyroidism and senile bone loss; 4) on the basis of the data from rats fed a soy protein-containing diet, a decline in renal function and progressive hyperparathyroidism are not inevitable consequences of aging in the ad libitum fed rats.