The formation of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) after single intravenous injections of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) was examined in four patients with chronic renal failure on regular haemodialysis. Following 1-3 micrograms 1 alpha-OHD3, administered at weekly intervals, 1,25-(OH)2D3 appeared in the circulation within 1 h, and peak concentrations were reached between 2 h and 5 h. By 8 h serum 1,25-(OH)2D3 concentrations had started declining and by 44 h they had returned to baseline after 1 microgram 1 alpha-OHD3, but they were still above basal after 2 and 3 micrograms by an average of 30 pmol/l. One week after injections, concentrations were back to basal in all patients studied. The serum 1,25-(OH)2D3 dose response to injected 1 alpha-OHD3 was linear, indicating ample capacity of the liver 25-hydroxylase to further hydroxylate 1 alpha-OHD3. However, examination of the individual responses revealed lower increments in serum 1,25-(OH)2D3 concentrations in the patients with the highest basal serum 25-hydroxyvitamin D concentrations. Intravenous 1 alpha-OHD3 may be useful in the further study of the interactions between 1,25-(OH)2D3, calcium and PTH in chronic renal failure, as well as of the hepatic metabolism of vitamin D.