We report our observations over 18 years (1970-1988) on 81 compliant patients with resistant ulcerative colitis who received 91 courses of treatment with 6-mercaptopurine (6-MP) for at least 4 months. These represent 172 patient years of 6-MP therapy and 308 years of observation after initiating 6-MP. In all patients, treatment with sulfasalazine and steroids had failed; most (96%) were dependent on systemic steroids and still symptomatic. The mean treatment period with 6-MP was 1.8 yr. In 42 out of 87 courses (48%) of 6-MP steroids could be eliminated, and in another 11 (13%) could be significantly reduced, for a total response rate of 61%. When four patients not on steroids were included, the response rate was 63%. The steroids were discontinued after a mean treatment time of 10 wk, and the 42 patients remained steroid free for the remainder of 6-MP treatment. Follow-up data after discontinuing 6-MP in 29 patients from this group show the mean time to relapse was 21 months with a median time of 12.5 months. We conclude that 6-MP is effective in inducing remission, eliminating steroids, and maintaining remission in many patients with refractory ulcerative colitis. Patients should be made aware of this option before colectomy is recommended.