To explore the changes in the relationship between skeletal and Ca2+ homeostasis with age, we studied 50 dogs divided into four age groups. The skeletal uptake of 85Sr decreased markedly with age, and the immunoreactive parathyroid hormone (iPTH) level increased. There was a significant correlation between iPTH value and the calculated short-term exchange of Ca in bone (r = 0.55; p less than 0.001). Bone formation and bone resorption decreased with age except that in the oldest group of dogs the resorption increased (p less than 0.001). We suggest that in aging dogs the skeletal exchange of Ca falls to a very low level that decreases the immediate effect of PTH and thus leads to a chronic net increase in circulating PTH. Concomitant with this is an increase in osteoclastic bone resorption and, over a long time, loss of skeletal mass.