We measured serum concentrations of 1,25(OH)2-vitamin D3, 25(OH)-vitamin D3, parathyroid hormone (PTH), and uric acid in 114 male patients with primary gout and 51 normal male control subjects. Serum 1,25(OH)2-vitamin D3 was significantly lower in patients with gout compared with control subjects (38.4 +/- 11.9 v 44.4 +/- 11.0 pg/mL, P < .005), whereas no differences were observed between the two groups for serum 25(OH)-vitamin D3 or PTH. Serum uric acid was significantly higher in patients with gout versus control subjects (8.8 +/- 1.3 v 5.7 +/- 1.0 mg/dL, P < .0001). In addition, there was a significant negative correlation between serum uric acid and 1,25(OH)2-vitamin D3 concentrations (r = .17, P < .05). Administration of allopurinol or benzbromarone to the patients for 1 year caused a significant increase in serum 1,25(OH)2-vitamin D3, which was associated with a significant decrease in serum uric acid. In contrast, 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 serum 1,25(OH)2-vitamin D3 in patients with gout by inhibiting 1alpha-hydroxylase activity.