Purpose: Catechol-O-methyl transferase (COMT) is an enzyme responsible for the degradation of catecholamines, which have been implicated in the pathophysiology of Irritable Bowel Syndrome (IBS). The COMT val158met polymorphism (rs4680) is a functional single-nucleotide polymorphism that results in a valine-to-methionine substitution at codon 158. The low activity met allele has been associated with higher sensory and affective ratings of pain than the high activity val allele. We sought to explore a possible association of the COMT val158met polymorphism with IBS symptoms, abdominal pain, and bowel patterns. Methods: Women diagnosed with IBS (Rome II criteria) were recruited for this study (age 17-80, n=51). They had high abdominal pain scores (Rome II A2 ≥3 and A9≥3) and ≥ 25% days per month with pain. Subjects recorded symptoms in a daily diary for 28 days and also completed an SCL-90-R. Subjects with organic GI diseases were excluded. Subjects were matched against age-related controls without bowel symptoms. DNA was isolated from buccal swabs in subjects and from buffy coat preparations of whole blood in controls, and the COMT genotype was determined by PCR-based assay. Results: Although the alleles were distributed evenly throughout both the IBS and control groups, we found a trend for IBS patients to be met/met genotype vs. controls (n= 15, n=9, p=.136). Among the IBS group: 1) There was no difference in Rome II abdominal pain scores between genotypes. 2) Of met/met (n=15), 67% were more likely to have diarrhea predominant symptoms compared to val/val or val/met. 3) met/met was associated with greater daily GI symptoms than val/val and val/met [abdominal discomfort after eating, p=.017; abdominal distension, p=.048; intestinal gas, p=.048; flatulence, p=.05; and bloating, p=.061]. 4) Gas symptom composite increased with increasing Global Severity Index (GSI) score [p=0.006], gas increased with increasing fatigue [p=0.028], and abdominal pain after eating increased with both increasing GSI [p=0.017] and fatigue [p=0.044]. 5) met/met had a higher percentage of days with pain after eating [p=.023]. Conclusion: Our results demonstrate that the met/met genotype is associated with increased GI symptoms in patients with IBS. While there was no statistically significant difference in genotypes between IBS and control groups or Rome II abdominal pain scores among the IBS group this could be attributed to small study size and that IBS subjects were chosen for ‘high pain’ symptoms, thereby limiting variance. Our results indicate that further investigation is needed to describe the role of the COMT enzyme in IBS.