Active vitamin D3 is used commonly in hemodialysis patients with severe secondary hyperparathyroidism. Intermittent pulse therapy with active vitamin D3, either orally or intravenously, has been proven to be effective with less hypercalcemic complication than daily oral vitamin D3. We therefore designed a three-phase crossover study to compare the effect of oral and intravenous calcitriol given by intermittent pulse therapy. Thirteen regular hemodialysis patients were enrolled. In phase 1, 1 microgram calcitriol was given orally at bedtime twice a week for 4 months, and then was stopped for 1 month to washout. In phase 2, 1 microgram calcitriol was given intravenously immediately after hemodialysis twice a week for 2 months, and then was stopped for 1 month to washout. Phase 3 repeated phase 1 but lasted for only 2 months. Calcium carbonate was given as the sole phosphate-binding agent if there was no severe hypercalcemia or hyperphosphatemia. Serum parathyroid hormone (PTH) levels decreased dramatically in all three phase therapies. As a result, mid-molecule PTH decreased from 5.71 +/- 2.65 to 3.97 +/- 2.92 ng/ml in phase 1 (p = 0.010), from 4.34 +/- 3.39 to 1.98 +/- 1.76 ng/ml in phase 2 (p = 0.007), and from 2.72 +/- 0.97 to 1.67 +/- 0.71 ng/ml in phase 3 (p = < 0.001). However, there was no difference in the calculation of the PTH declination among the three phases (32, 50 and 42%, respectively). The incidence of hypercalcemia was higher in using calcitriol than without it (23 vs. 6%, p < 0.05), but there was no difference between intravenous and oral calcitriol (35 vs. 19%). The above results suggested that both oral and intravenous calcitriol, with lower doses and intermittent pulse therapy, were equally effective in controlling secondary hyperparathyroidism. The incidences of hypercalcemia were similar in both oral and intravenous calcitriol using 3.5 mEq/1 dialysate calcium concentration and calcium carbonate as the chief phosphate binder.