The responses to inhalation of 35% carbon dioxide (CO(2)) as a stressor were compared in female irritable bowel syndrome (IBS) patients and healthy controls to assess potential differences in cardiovascular, neuroendocrine and behavioural responses to stress. A total of 22 women (12 patients with ROME II defined diarrhoea-predominant IBS and 10 aged-matched controls) were challenged with a single vital capacity breath of 35% CO(2) (with 65% oxygen). Beat-to-beat blood pressure and heart rate were recorded prior to, during and after the inhalation. Serum cortisol concentration and behavioural ratings were measured pre- and post-inhalation. A typical pattern of responses to CO(2) was observed, characterised by a reduction in heart rate and increases in serum cortisol and anxiogenic symptoms; however, these responses did not differ between groups. Both groups also demonstrated an increase in systolic blood pressure; however, this response was significantly enhanced in IBS patients compared to healthy controls (P < 0.05). These findings demonstrate that females with diarrhoea-predominant IBS have an exaggerated pressor response to 35% CO(2) stress challenge, suggesting a more stress-responsive sympathetic nervous system.