OBJECTIVES: Irritable bowel syndrome (IBS) is a functional disorder that is associated with a number of extra-intestinal co-morbidities and a pro-inflammatory profile. This study was designed to examine the cytokine profile among a group of IBS patients with the extra-intestinal co-morbidities fibromyalgia, premenstrual dysmorphic disorder, and chronic fatigue syndrome. METHODS: In all, 100 female IBS patients with these co-morbidities, 21 IBS subjects without co-morbidity (''pure'' IBS; Rome II), and 54 age-matched female controls took part in the study. Blood was drawn for measurement of the plasma cytokines interleukin (IL)-1 beta, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)alpha, and interferon gamma. The presence of the selected extra-intestinal manifestations was assessed using standard international criteria. RESULTS: Patients with IBS have increased plasma levels of IL-6 and IL-8; those with these extra-intestinal co-morbidities were found to have, in addition, increased levels of IL-1 beta and TNF alpha. No associations were evident between cytokine profiles and the nature of the co-morbidity or number of extra-intestinal co-morbidities present. CONCLUSIONS: Although IBS is characterized by a pro-inflammatory profile featuring the pro-inflammatory cytokines IL-6 and IL-8, IBS patients with certain extra-intestinal co-morbid conditions are distinguished by additional elevations in IL-1 beta and TNF alpha.