The effects of dietary calcium intake on the composition and turnover of the femur and humerus were compared in two mouse strains that differ in growth kinetics and phorbol ester-induced signal transduction. C57BL/6 (control) and SENCAR (large) mice were fed calcium-deficient (0.02% Ca) or -sufficient (0.6% Ca) diets from 10 to 14 weeks of age. Bone mass was determined gravimetrically. Calcium and magnesium were determined by atomic absorption spectrophotometry, while phosphorus was determined colorimetrically. Turnover was estimated pharmacokinetically in [3H]tetracycline-labeled bone. Femur and humerus lengths, breadths, masses, and ash and mineral contents were higher in SENCAR mice than in C57BL/6 mice at 10 weeks of age and after being fed 0.02% or 0.6% calcium diets for four weeks. Relative formation was higher in C57BL/6 mice than in SENCAR mice from 10 to 14 weeks of age, resulting in greater net increases (0.6% Ca diet) or lower net decreases (0.02% Ca diet) in the calcium contents of the femurs and humeri of C57BL/6 mice, compared to SENCAR mice. Calcium-deficient feeding stimulated higher relative rates of bone resorption in both strains and affected the net changes in bone calcium contents. Thus, hereditary factors in SENCAR and C57BL/6 mice that regulate formation rates, not resorption rates or the response to dietary calcium intake, appear to modulate net changes in humerus and femur calcium contents at maturity.