We evaluated the effects of dietary PO4 restriction on 25-OH-Vitamin D3 metabolism, serum iPTH levels, and mineral balances in healthy women and men. PO4 balances were progressively negative because of fecal losses without sex difference. Turnover of the plasma 25-OH-D pool was increased from 5.8 +/- 0.4 to 12 +/- 1.2 nmol/day; P less than 0.001, despite a fall in serum iPTH of -1.1 +/- 0.3 mulEq/ml; P less than 0.01. In both sexes, net intestinal calcium and magnesium absorption increased in proportion to a more rapid turnover of the plasma 25-OH-D pool, implying increased renal 1,25-(OH)2-D3 production. By contrast, there was a striking sex difference in the response of serum PO4 to dietary PO4 deprivation; the levels falling progressively in women, but remaining at control levels in men. Women demonstrated progressive hypercalciuria and negative Ca balances while in men the increments in intestinal Ca absorption were approximately matched by the increments in urinary Ca excretion so that Ca balances were not different from zero.