To determine the influence of aging on the relative roles of parathyroid hormone (PTH) and calcitonin in the control of calcium homeostasis during fasting, we assessed changes in plasma calcium in fasted rats following simultaneous removal of the glands that secrete both hormones. Animals ranging in age from 3 to 34.7 wk were thyroparathyroidectomized or sham operated and bled by orbital puncture prior to and 1.5, 3, and 6 h after surgery. After thyroparathyroidectomy (TPTX), plasma calcium fell immediately and progressively in very young rats (3-6 wk old); in young animals (6.5-9.4 wk old), there was a delay of about 1.5 h pceded by a rise, which persisted for at least 3 h. Since the rise and fall in plasma calcium after TPTX are most likely due to calcitonin and PTH deficiencies, respectively, our observations are consistent with the following hypothesis; in the fasting state, the relative importance of calcitonin and PTH in the regulation of plasma calcium varies with age; PTH appears to play the dominant role in young rats; however, during maturation the importance of calcitonin appears to increase progressively.