OBJECTIVE: The pathogenesis of irritable bowel syndrome (IBS) is probably multifactorial with dysfunction at different levels of the brain-gut axis. The aim of this study was to evaluate an existing biobehavioral model of IBS symptom generation in a large group of patients. MATERIAL AND METHODS: In 104 IBS patients, we assessed symptom severity by a symptom diary, visceral hypersensitivity using a barostat, autonomic function by measuring arterial baroreflex sensitivity and psychological functioning using questionnaires. Structural equation modeling was used to calculate the reciprocal and chronological relationships between the model variables. RESULTS: Analysis of the adjusted original model indicated poor fit [Satorra-Bentler chi=28.47; degrees of freedom (df)=11, P<0.01; comparative fit index (CFI)=0.78], which was caused by omission of two paths (illness behavior-IBS symptoms and trauma-IBS symptoms). The revised model yielded a reasonable fit (chi=13.88, df=9, P=0.13; CFI=0.94). The model explained 18.7% of the variance in IBS symptoms. Illness behavior completely mediated the effect of cognitions on IBS symptoms and partly mediated the effect of trauma on IBS symptoms. The fit of this alternative model was good (chi=9.85, df=8, P=0.28; CFI=0.98). The alternative model explained 20.0% of the variance in IBS symptoms. CONCLUSION: The proposed biobehavioral model could not be validated. Although visceral hypersensitivity and IBS symptom severity significantly correlate, autonomic function and IBS symptoms do not. Cognitive-behavioral aspects are important in the clinical expression of IBS, with illness behavior playing an intermediate and central role.