The acute effects of a single intravenous injection of 2 mu g of 1 alpha-hydroxycholecalciferol (alfacalcidol) were studied for a 24-h period in six normal males (mean age 33 years), six women with primary hyperparathyroidism (mean age 72 years) and six women with established osteoporosis (mean age 63 years). In all three groups, serum calcitriol levels rose to a peak 2-3 h after administration of alfacalcidol. Basal levels were highest in the primary hyperparathyroidism group at (mean+/-SEM) 81+/-2 vs 62+/-12 (normal males) (p<0.05) and 56+/-5 pmol/l (osteoporosis) (p<0.01). Highest peak levers were found also in the primary hyperparathyroidism group at 150+/-15 vs 114+/-15 (normal males) (p<0.05) and 127+/-15 pmol/l (osteoporosis) (p<0.01). The rise in calcitriol was higher in the primary hyperparathyroidism group than either the normal males or osteoporotic patients (p<0.05). No significant differences were evident in basal serum calcidiol concentrations among the three treatment groups. As might be expected, highest basal concentrations of parathyroid hormone (PTH), serum calcium and serum osteocalcin were noted in the primary hyperparathyroid group (PTH: 17.1+/-7.7 vs 1.9+/-0.5 (normal males) (p<0.01) and 2.1+/-0.3 pmol/l (osteoporosis) (p<0.01); calcium: 3.06+/-0.08 vs 2.50+/-0.02 (normal males) (p<0.01) and 2.43+/-0.02 mmol/l (osteoporosis) (p<0.01); osteocalcin: 1.10+/-0.08 vs 0.56+/-0.16 (normal males) (p<0.05) and 0.53+/-0.21 nmol/l (osteoporosis) (p<0.05). Following treatment with alfacalcidol, no significant change was observed in PTH, calcium or osteocalcin serum concentrations in any group. These results show that maximal conversion of alfacalcidol to calcitriol occurs within a few hours of administration of alfacalcidol in normal males and patients with primary hyperparathyroidism and osteoporosis. Whilst this may reflect differences in activity of the enzyme 25-hydroxylase among these groups, other explanations, such as differences in calcitriol clearance, cannot be excluded.