We report our observations after 20 yr of clinical experience with 6-mercaptopurine (6-MP) in 148 patients with Crohn's disease who had not satisfactorily responded to steroids and other drugs. Specific therapeutic goals were established for each patient, and the NFIC (now CCFA)-IOIBD index of Crohn's disease activity was calculated pre- and post-therapy. Defined therapeutic goals were achieved in 68%. Major successes include 1) elimination of steroids (66% p < 0.001); 2) healing of internal fistulas and abscesses or improvement by elimination of discharge and tenderness (64% p < 0.05); and 3) healing or improvement by elimination of pain, tenderness and discharge of perirectal fistulas and abscesses (87%, p < 0.05). Other therapeutic goals which achieved 100% success were 1) healing or marked improvement of Crohn's disease of the stomach and duodenum; 2) permitting surgery to be performed electively after 6-MP allowed margins for surgical resection to be delineated. 6-MP was less effective in achieving the therapeutic goals of preventing recurrent small bowel obstruction (43%) and elimination of abdominal masses (55%). Seventy-eight percent of patients showed a reduction in the activity index with a mean of 43% (95% C.I. 36-51%). 6-MP was once again demonstrated to be effective in achieving major therapeutic goals in two of three patients with severe Crohn's disease. Accordingly, the need for surgical resection and subsequent extension of the disease is often postponed or eliminated.