Standard therapy with orally administered active metabolites of vitamin D3 often does not satisfactorily control the biochemical manifestations of secondary hyperparathyroidism in uremic patients. This may be due to inadequate serum concentrations of 1,25 (OH)2D3 achieved during the treatment. Eighteen patients on chronic hemodialysis (HD) with severe hyperparathyroidism were given high doses of calcitriol (1,25 (OH)2D3) or alphacalcidol (1 alpha-OH-D3) orally, in ten evenings preceding each HD session. The effect of the treatment on circulating parathyroid hormone (PTH), serum hydroxyproline, serum alkaline phosphatase and bone isoenzyme was examined in a pilot study during 5 weeks. Irrespective the preparation given the treatment caused 71.7 +/- 22.2% reduction of intact serum PTH concentration with only moderate rise of serum calcium. A decrease of serum hydroxyproline and activity of alkaline phosphatase with its bone fraction, the direct indexes of bone turnover reduction, was also observed. With ongoing calcium carbonate therapy (3-6 g/day) 5 episodes of mild, asymptomatic hypercalcemia was observed for the 108 times of the total number of examinations; in those cases the dose of alphacalcidol was reduced. Our observations indicate that intermittent administration of 1,25 (OH)2D3 as well as 1 alpha-OH-D3 in high oral doses effectively suppress PTH synthesis in uremic hyperparathyroidism already in a couple of weeks. The effect is similar to that obtained with intravenous administration of the vitamin D3 active metabolites.