Studies were carried out to characterize the secretion and the effects of calcitonin in the Buffalo rat. Mean basal concentrations of calcitonin and parathyroid hormone were significantly increased in serum of rats older than 6 months of age as compared with rats between 2 and 3 months of age. The mean concentration of calcium in serum was independent of age. In both age groups, serum calcitonin was increased by administration of calcium (1 mmol/kg body wt) or isoproterenol (100 microgram/kg body wt), was diminished by beta-adrenergic blockade with DL-propranolol (1 mg/kg body wt) and was not altered by either pentagastrin or glucagon (200 and 100 microgram/kg body wt respectively). The average weight of the thyroid glands was significantly greater in the old than in the young animals but the mean concentration of calcitonin in the thyroids was the same. Thyroparathyroidectomy produced a transient increase followed by a fall in mean serum calcium in the old rats. In contrast, a progressive decline in the mean concentration of calcium in serum was observed after thyroparathyroidectomy in the young rats. Treatment of old animals with reserpine (2.5 mg/kg body wt) markedly depleted noradrenaline in the thyroid, lowered calcitonin in serum and converted the pattern of response of serum calcium to thyroparathyroidectomy to that observed in young animals. The results provide evidence that hypercalcitonaemia occurs in aged Buffalo rats, as does hyperparathyroidism, and that the concentrations of calcitonin in blood are modulated by beta-adrenergic affectors. Glucagon and pentagastrin exhibit little if any effects on calcitonin secretion in this strain of rat regardless of age.