The relationship between histologic changes at resection margins and anastomotic recurrence was evaluated in patients with Crohn's disease. Pathology and medical records from 1960 to 1977 identified 100 patients who met the following criteria: 1) no prior surgery for Crohn's disease, 2) small bowel or small bowel and colonic resection with anastomosis done for Crohn's disease at the Cleveland Clinic, and 3) resection margins available for microscopic analysis. The following histologic features of the margins were evaluated: edema, inflammation, lymphoid aggregates, pyloric metaplasia, fibrosis, cryptitis and crypt abscesses, ulcers, granulomas, villous shortening, mucin depletion, neuronal hyperplasia, and transmural inflammation. Additionally, margins were categorized as histologically normal, showing nonspecific changes, showing changes suggestive of Crohn's disease, and showing changes diagnostic for Crohn's disease. Anastomotic recurrence occurred in 50 patients after an average follow-up period of 11.5 years. Cumulative recurrence-free rates for the four margin categories were not significantly different. Anastomotic recurrence was not associated with any clinical or histologic feature or combination of features.