The effect of intravenous 1α(OH)D<sub>3</sub> on circulating intact parathyroid hormone (PTH) and COOH-terminal immunoreactive PTH was examined in 21 patients on chronic hemodialysis. The patients were treated for 3 months with increasing doses of 1α(OH)D<sub>3</sub> under careful control of serum Ca<sup>2+</sup>. 1α(OH)D<sub>3</sub> was given intravenously at doses of up to 4 μg three times a week, and blood samples were obtained every week, including 1 week before treatment (basal control). No patients were treated with oral vitamin D metabolites. At the end of the study intact PTH levels were reduced by an average of 67 ± 6%, and COOH-terminal immunoreactive PTH levels were reduced by 35 ± 6%. Serum Ca<sup>2+</sup> was kept within normal levels, but showed a slight increase from 1.17 to 1.30 rnmol/l. An effect of calcium on PTH secretion could not be excluded, but an effect of 1α(OH)D<sub>3</sub>, independent of serum Ca<sup>2+</sup> was also found. This effect may be mediated by 1,25(OH)<sub>2</sub>D<sub>3</sub>, assuming a large capacity of the 25-hydroxylase in the liver to convert 1α(OH)D<sub>3</sub> to 1,25(OH)<sub>2</sub>D<sub>3</sub>. Also, the parathyroid glands may possess receptors for 1α(OH)D<sub>3</sub> with an effect similar to that established for the 1,25(OH)<sub>2</sub>D<sub>3</sub> receptors. Thus, although the exact mechanisms ofthe action of 1α(OH)D<sub>3</sub> have not yet been completely clarified, it is concluded that intravenous administration of 1α(OH)D<sub>3</sub> may be of benefit in the treatment of secondary hyperparathyroidism of uremia.