Objective: Depression has been linked to irritable bowel syndrome (IBS), but the mechanism underlying this relationship is unknown. This cross-sectional study explores the possibility that negatively skewed beliefs patients hold regarding abdominal pain (ie, catastrophizing) mediate the relationship between depression and pain severity. Methods: The sample included 244 consecutively evaluated individuals who met Rome II diagnosis for IBS without comorbid gastrointestinal disease and completed measures of pain severity, trait anxiety, catastrophizing, maladaptive beliefs, and depression as part of baseline assessment of an National Institutes of Health-funded randomized controlled trial of 2 nondrug treatments. Results: Using a mediational model involving a series of linear regressions, results indicated that pain catastrophizing partially mediated the link between depression and abdominal pain severity. Depression, catastrophizing, and control variables accounted for 21% of the variance in pain severity. The finding that patients with IBS with greater depression reported greater pain severity can be partially explained by their tendency to engage in more catastrophic thinking specific to pain. Conclusions: The relation between depression and pain is not, as psychogenic models predict, strictly a direct and linear one but works partly through patients' beliefs regarding their pain in general and pain catastrophizing in specific. Implications of the findings for understanding and investigating the depression-IBS link from a biopsychosocial perspective are discussed.