To test the effectiveness of 6-mercaptopurine (6-MP) in the treatment of Crohn's disease, we entered 83 chronically ill patients into a two-year double-blind study comparing 6-MP with placebo. Crossover data showed that improvement occurred In 26 of 39 courses of 6-MP (67 per cent) as compared with three of 39 courses of placebo (8 per cent) (P<0.0001). Non-crossover data likewise confirmed the superiority of 6-MP. The drug was more effective than placebo in closing fistulas (31 vs. 6 per cent) and in permitting discontinuation or reduction of steroid dosage (75 vs. 36 per cent) (P<0.001). The onset of response to 6-MP was often delayed, with 32 per cent of patients taking longer than three months to respond, and 19 per cent taking longer than four months. Adverse side effects to 6-MP occurred in 10 percent of patients and were uniformly reversible. We conclude that 6-MP is an effective and useful agent in the management of Crohn's disease. (N Engl J Med. 1980; 302:981–7.)