We measured the serum concentrations of 1,25(OH)2-vitamin D3, 25(OH)-vitamin D3, parathyroid hormone (PTH) in 82 male patients with primary gout whose serum uric acid was significantly higher than that of 41 normal control male subjects (8.8 +/- 0.2 vs 5.6 +/- 0.2 mg/dL, p < 0.001). The serum 1,25(OH)2-vitamin D3 concentration was significantly lower in the patients with gout compared with the control subjects (39.6 +/- 1.4 vs 44.8 +/- 1.7 pg/mL, p < 0.05), while no differences were observed between the two groups in either the serum concentration of 25(OH)-vitamin D3 or PTH. The administration of uric acid lowering agent to the patients for 1 year caused a significant increase in their serum 1,25(OH)2-vitamin D3 concentration which was associated with a significant decrease in their serum uric acid concentration. In contrast, the serum concentrations of 25(OH)-vitamin D3 and PTH were not affected by these drugs. These results suggest that uric acid per se may directly decrease the serum concentration of 1,25(OH)2-vitamin D3 in patients with gout by inhibiting 1-hydroxylase activity.