Colono-ileoscopy was performed on 11 patients after ileocolic resection for Crohn's disease, to observe development of recurrent anastomotic inflammation and its relationship to mucosal phospholipase A2 (EC 3.1.1.4) activity. Ileal inflammation appeared soon after surgery in eight cases but in none of nine controls with noninflammatory bowel disease. The ileal inflammation was more severe 1-3 cm above than greater than 5 cm above the ileocolic junction (p less than 0.05), whereas the postanastomotic colonic mucosa remained unchanged. Ileal phospholipase A2 activity in the mucosa was equally raised at the two ileal sites (p less than 0.01 and less than 0.02), irrespective of the presence or absence of inflammation. In colonic postanastomotic mucosa the phospholipase A2 activity was the same as in the controls. Further followup showed preanastomotic ileal inflammation at both investigated levels in all patients with Crohn's disease but still with greater severity close to the mucosal junction (p less than 0.05). The study indicates that recurrent inflammation in Crohn's disease is initiated in the terminal ileum close to the ileocolic junction. Progression of severity is accompanied by greater proximal involvement. The increase in mucosal phospholipase A2 activity, which precedes endoscopically detectable inflammation, implies a role for this enzyme in Crohn's disease.