Both intermittent intravenous and intermittent oral calcitriol have been shown to be effective in the treatment of secondary hyperparathyroidism in hemodialysis patients and it has been claimed that intravenous calcitriol causes less hypercalcemia. However, there has been no published systematic comparison of the two routes of administration of intermittent calcitriol. Therefore in a prospective crossover study 11 (9 male) patients on maintenance hemodialysis were randomized to receive intravenous followed by oral calcitriol for 4 months each, or oral followed by intravenous calcitriol, commencing at 2 micrograms postdialysis three times per week. Initial serum immunoreactive parathyroid hormone (PTH) was 446 +/- 111 (normal < 65) pg/ml. Calcium-containing phosphate binders were not used. Calcitriol was ceased if hypercalcemia developed and restarted at 2 micrograms or 1 microgram when calcium returned to normal. Hypercalcemia was frequent (11 episodes in 8 patients on intravenous calcitriol and 10 episodes in 7 patients on oral calcitriol) and dose reduction to 1 microgram was necessary in 7 patients on intravenous and on 6 patients on oral. Serum PTH fell during both treatments. Parathyroid enlargement was seen in 10 glands from 4 patients, but no size reduction was demonstrated with treatment. There was no reduction in activity on quantitative metabolic bone scan. In summary, intermittent oral calcitriol and intermittent intravenous calcitriol were equally effective in reducing serum parathyroid hormone levels and at a dose of 2 micrograms postdialysis caused hypercalcemia with equal frequency.