Background: Our aim was to explore the relationships among perceived stress, intestinal inflammation, and inflammatory bowel disease (IBD) symptoms over time. Methods: Participants were recruited from a population-based registry of persons with IBD and assessed at months 0, 3, and 6. Key dependent measures were the Manitoba IBD Index (symptom activity), Cohen's Perceived Stress Scale, and fecal calprotectin in stool (intestinal inflammation). Results: Complete data were available for 417 participants at months 0; 369 provided follow-up data. Active symptoms were reported by 54% of those with Crohn's disease (CD) and 40% of those with ulcerative colitis (UC) and approximately one-third consistently had fecal calprotectin measures >= 250 mu g/g, suggestive of active inflammation. A significant proportion of participants had indications of inflammation but no active symptoms over the 6 months. Correlations of month 0 perceived stress and disease activity measures with values at months 3 and 6 for both CD and UC indicated strong temporal stability. In hierarchical multiple regression analyses, month 0 symptom activity was thus a strong predictor of later symptom activity for CD and UC. Perceived stress predicted change in symptom activity from 0 to 3 months for CD, as did use of prednisone for UC. Comparably, month 0 perceived stress was a strong predictor of later perceived stress for CD and UC, while month 0 symptom activity predicted change in perceived stress from 0 to 3 months for both CD and UC. Conclusions: The analysis revealed prospective bidirectional relationships between perceived stress and IBD symptoms but no relationship between perceived stress and change in intestinal inflammation as assessed by fecal calprotectin.