The pathophysiology of irritable bowel syndrome (IBS) is complex and incompletely known. Very little has been studied regarding the role of submucous neuronal activity. We therefore measured small intestinal transmural potential difference (PD, reflecting mainly electrogenic chloride secretion), and its linkage with fasting motor activity [migrating motor complex (MMC)] in controls (n = 16) and patients with IBS [n = 23, 14 diarrhoea predominant (d-IBS) and nine constipation predominant (c-IBS)]. Transmural-PD and its relation to MMC phase III was measured by modified multilumen manometry for 3 h in the fasting state using one jejunal and one duodenal infusion line as flowing electrodes. The amplitude and duration of motor phase III was similar in controls and IBS patients, but the propagation speed of phase III was higher in IBS patients. In IBS patients, maximal PD during MMC phase III was significantly elevated in both the duodenum and jejunum (P < 0.05) and the PD decline after phase III was significantly prolonged in the jejunum (P < 0.01). The PD elevation was seen in both duodenum and jejunum in d-IBS patients, but only in the jejunum in the c-IBS patients. On the basis of previous modelling studies, we propose that the enhanced secretion may reflect disturbed enteric network behaviour in some patients with IBS.