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Serum iPTH was measured in a large series of normal and osteoporotic women as a function of age, with radioimmunoassays using three antisera: GP-1M, which recognizes primarily a region within the 44--68 amino acid sequence of PTH; CH-12M, which appears to recognize primarily intact hormone; and CH-14M, which recognizes primarily a region within the 1--34 amino acid sequence of PTH. In normal women 20 to 90 years of age, serum iPTH increased significantly with age (p less than 0.001); the proportional increase was greater when measured with antiserum GP-1M (80%) than when measured with antiserum CH-12M (30%), which suggests that the increase in circulating carboxyl fragments of PTH was greater than the increase in circulating intact PTH. In 40 patients with postmenopausal osteoporosis, the mean value for serum iPTH assayed by antiserum GP-1M did not differ significantly from that for age-matched normal women; however, three osteoporotic patients had elevated values and thus appear to represent a separate population. When these subjects were excluded, mean serum iPTH assayed by antiserum GP-1M also was lower than normal (p less than 0.001). The mean value for serum iPTH was lower in osteoporotic patients than in normal subjects when assayed by either antiserum CH-12M (p less than 0.001) or antiserum CH-14M (p less than 0.001). Values for serum phosphate and renal tubular phosphate resorption, both indices of PTH function, were increased (p less than 0.005) in the osteoporotic subjects. Although creatinine clearance decreased with age in both normal and osteoporotic subjects, partial correlations with age held constant showed no relationship between creatinine clearance and serum iPTH. This suggests that a decrease in renal function was not the major factor accounting for the rise in serum iPTH with age. We conclude that serum iPTH increases with aging but that for any given age, it is either normal or low in patients with postmenopausal osteoporosis.