The relationship between distal duodenal motility, fluid transport and transmural potential difference (PD) was studied in 33 healthy volunteers. Motor activity was registered with a low-compliance pneumohydraulic system; one pressure channel also served as an intraluminal flowing electrode for registration of transmural PD. Net fluid and bicarbonate transport were measured with a triple lumen perfusion technique. The relation between net fluid transport (NFT) and transmural PD depended on the current phase of the migrating motor complex (MMC). In phase I and early phase II (low motor activity), a significant net fluid absorption was seen when the perfusate contained glucose (30 mM). If glucose was substituted with mannitol, NFT was not significantly different from zero and transmural PD was slightly lumen positive. In the early part of the MMC cycle (low motor activity), there was a significant correlation between a more lumen negative transmural PD and a higher net fluid absorption in individual experiments (r = -0.65; P < 0.01). In late phase II of the MMC cycle (high motor activity), NFT changed significantly in the secretory direction in both Krebs mannitol and Krebs glucose perfused segments, and the perfusate-related difference in transport rate was no longer statistically significant. In the Krebs mannitol group, transmural PD became significantly more lumen negative, and there was also a decrease in net bicarbonate absorption as well as a slight acidification of the luminal contents. The relationship between transmural PD and NFT was reversed, i.e. a more lumen negative PD was associated with a higher net fluid secretion in individual experiments (r = 0.82; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)