In a double-blind study, we examined the efficacy of allopurinol in the prevention of recurrent calcium oxalate calculi of the kidney. Sixty patients with hyperuricosuria and normocalciuria who had a history of calculi were randomly assigned to receive either allopurinol (100 mg three times daily) or a placebo. After the study, the placebo group had 63.4 percent fewer calculi (P less than 0.001), whereas the allopurinol group had 81.2 percent fewer calculi (P less than 0.001). During the study period, the mean rate of calculous events was 0.26 per patient per year in the placebo group and 0.12 in the allopurinol group. When the treatment groups were compared by actuarial analysis, the allopurinol group was found to have a significantly longer time before recurrence of calculi (P less than 0.02). We conclude that allopurinol is effective in the prevention of calcium oxalate stones in patients with hyperuricosuria. The large reduction in the frequency of calculi in the placebo group underscores the positive treatment bias that regularly occurs in trials of prophylaxis against renal calculi when historical controls are used.