Fistulae are distressing chronic complications of Crohn's disease which have served as one of the most common indications for surgical resection. While steroids and sulfasalazine have not been successful in closing fistulae, in a previous double-blind study 6-mercaptopurine (6-MP) was more effective than placebo in accomplishing this goal (31% vs 6%). Thirty-four patients with Crohn's disease fistulae were treated with 6-MP for a minimum period of 6 months. In 13 patients (39%) the fistulae closed completely, and in another 9 (26%) there was obvious improvement. All types of fistulae responded to 6-MP with the most impressive closures occurring in patients with fistulae of the abdominal wall and enteroenteric fistulae. The mean time to respond was 3.1 months, with 23% of patients taking longer than 4 months to show any response. Response was not related to other drugs (steroids, sulfasalazine) used in conjunction with the 6-MP. The site of intestinal involvement with Crohn's disease did not appear to play a significant role in the frequency or degree of response to 6-MP, but patients without prior resection and fistulae did better than those with fistulae occurring after surgery. The long-term response to fistulae was good if 6-MP was maintained, whereas exacerbation eventually followed discontinuation of 6-MP. 6-Mercaptopurine is an effective and useful drug in the treatment of fistulae, as it is in other manifestations of chronic unrelenting Crohn's disease.