Although 6-mercaptopurine is often used to treat adolescents with intractable Crohn's disease, its longterm efficacy has not yet been studied in this population. This study shows data derived from 36 adolescents (mean age ± SD, 16.5 ± 3.3 years; 27 males, 9 females) treated at least 6 months with 6-mercaptopurine (1.5 mg · kg-1 · day-1, maximum of 75 mg/day). Sites of Crohn's disease at the start of 6-mercaptopurine therapy included 17 ileocolic, 9 pancolic, 7 small bowel, and 3 partial colon. All had received corticosteroids, sulfasalazine, antibiotics, and nutritional support for 5.0 ± 3.0 years before administering 6-mercaptopurine, but intractable symptoms persisted. Disease activity lessened during the first year of 6-mercaptopurine, reflected by a higher Lloyd-Still disease activity score (pre, 64 ± 9 vs. 6-mercaptopurine, 72 ± 11; P < 0.0001). General activity, physical examination, nutrition, and laboratory subscores all improved (P < 0.004). Lessened disease activity occurred despite concomitant decrease in duration of prednisone use (pre, 9.5 ± 4.2 vs. 6-mercaptopurine, 6.6 ± 4.9 months/year; P < 0.001) and cumulative annual prednisone exposure (pre, 3672 ± 2106 vs. 6-mercaptopurine, 1964 ± 1460 mg; P < 0.0007). The frequency of perianal fistulae and abscesses also decreased (P < 0.01) during treatment. Annual rates of hospitalization decreased in 44% of subjects during 6-mercaptopurine treatment, while increasing in only 22%. Follow-up beyond 1 year of 6-mercaptopurine treatment showed continued remission in 23 of 30 subjects. No serious complications were seen. 6-mercaptopurine is an effective long-term therapy for adolescents with intractable Crohn's disease. While inducing remission, it also has a significant steroid-sparing effect which may be of particular benefit to this population. © 1990.