We investigated psychologic influences on duodenal ulcer by examining the effect of personality, stress, and mood, measured at diagnosis, on subsequent ulcer healing. Stressful life events, psychopathology (assessed using the Minnesota Multiphasic Personality Inventory), anxiety, depression, smoking, alcohol consumption, nonsteroidal antiinflammatory drug use, and serum pepsinogen I levels were determined immediately after endoscopy showed duodenal ulcer craters in 70 patients with recent onset of symptoms. Endoscopy was repeated following 6 weeks of ranitidine therapy. Six ulcers (8.6%) persisted, and the duodenum remained inflamed in an additional five cases, for a total of 16% with incomplete healing. The only baseline characteristic significantly associated with poor healing was anxiety (p = 0.03 for ulcer persistence, p = 0.02 for incomplete healing). Being in the highest anxiety tertile was associated with a more than fourfold elevation in the risk of incomplete healing (p = 0.02). The association between anxiety and poor healing was not changed by modification of the anxiety score to eliminate gastrointestinal symptom items or by adjustment for serum pepsinogen, sex, or cigarette smoking. Anxiety inhibits the healing of duodenal ulcers treated with adequate antisecretory therapy.