Improvement in Crohn's disease after drug therapy was evaluated in 38 patients with evidence of rectal disease at sigmoidoscopy in whom the rectum later appeared normal. Rectal biopsies taken before and after therapy were examined histopathologically. Cell counts of the lamina propria connective tissue cells were used to evaluate mucosal changes. The drugs apparently responsible for conversion of the rectal mocosal appearance to normal were sulfasalazine, prednisone, and 6-mercaptopurine.There was complete healing histologically in 24 patients (63%). In the other 14, healing was incomplete as evidenced by microscopic chronic inflammation, microgranulomas, or occasional lymphangiectasia. There were both complete and incomplete responses to all three drugs, but the total numbers were too small to identify significant therapeutic differences. Cell counts confirmed the elimination of acute inflammation. Despite drug therapy, histological evidence of activity persisted in one-third of the patients in whom the appearance of the rectum became normal.