The effects of age, sex, renal function, and seasonal variation on serum parameters within the vitamin D endocrine system were studied cross-sectionally in a healthy population of 167 men and 114 women, aged 20-94 yr. Serum 25-hydroxy- and 1,25-dihydroxyvitamin D [25OHD and 1,25-(OH)2D] did not decline with age in either sex. Nonlinear regression using a sine function showed a significant seasonal variation in 25OHD and 1,25-(OH)2D in both sexes (P less than 0.005). Serum intact PTH increased significantly by 35% over the age span in both sexes (P less than 0.005). In women, serum phosphorus and total and ionized calcium remained constant with age. In sharp contrast, males had a marked 25% fall in phosphorus across the age span (r = -0.564; P less than 0.0001) and a slight but significant 4% decline in total and ionized calcium. Creatinine clearance declined markedly with age, but was not related to 1,25-(OH)2D in either sex. Only in men was there a significant but modest inverse relationship between creatinine clearance and PTH (r = -0.212; P less than 0.05), which was multicollinear with age. We conclude that in healthy individuals 1) compromised vitamin D status or serum 1,25-(OH)2D levels are not a normal concomitant of aging; 2) declining glomerular filtration does not appear to be the principle cause of the age-related rise in PTH; and 3) there are marked male-female differences in phosphorus metabolism across the age span.