The effects of aging and estradiol on the concentration of plasma calcium in response to human calcitonin (hCT) were investigated in rats. Old (20 months) and young (2 months) female rats were catheterized via the right jugular vein and the left femoral vein before an infusion of 1 nM hCT (0.1 ml/min) into the left femoral vein. Young ovariectomized (Ovx) rats were injected subcutaneously with estradiol benzoate (EB, 25 micrograms/kg) or oil once daily for 3 days before hCT challenge. Blood samples were collected from the jugular catheter before and after the hCT infusion. The basal level of plasma calcium was not affected by age. The infusion of 1 nM hCT decreased the plasma calcium concentration by 18% in old and by 29% in young female rats. The post-infusion levels of plasma calcium were comparatively higher in old rats than in young rats (p less than .05 at 30 min and p less than .02 at 90 min). In young rats, the responses of plasma calcium to hCT infusion were reduced after ovariectomy. Short-term estrogen injection, however, did not restore the sensitivity of young Ovx rats to the CT infusion. These findings suggest that the plasma calcium level in response to calcitonin is decreased in rats during aging. The reduction of the hypocalcemic effect of calcitonin in old female rats at least was estradiol-independent.