The impact of psychological stress in recurrence of inflammatory bowel disease (IBD) is unclear. Why some patients with ulcerative colitis (UC) or Crohn's disease (CD) have unrelenting relapses whereas other IBD patients experience long periods of quiescent disease remains an enigma. The authors examined the risk of exposure to major stress events in clinical episodes of IBD. They followed up on 124 persons in a prospective study that monitored behavioral and biological characteristics for a period of 6 months. Stress-exposed subjects demonstrated increased risk of clinical episodes of disease when compared with unexposed subjects (RR = 2.6, 95% CI: 1.3-4.9). Elevated effect measures were highest for the domain of health-related stress (RR = 3.8, 95% CI: 1.5-9.9). In the multiple regression analysis, major stress events remained the most significant indicator of disease activity in the presence of the covariables considered. Only 7% of the variation in disease activity was uniquely attributed to stress. Baseline activity was the other notable indicator of subsequent disease activity in the study sample. All variables considered together explained 52% of the variance observed and implicated factors of potential clinical importance in monitoring recurrence of the disease.