The influence of lysophosphatidylcholine (LPC) on the permeability to different sized molecules in the stomach has been studied. Using a rat experimental model, we determined the gastric permeability to sodium fluorescein (molecular weight 376 dalton) and to fluorescein-labeled dextran 3000 (molecular weight 3000 dalton) in the absence or presence of LPC. We also examined the influence of LPC on the morphology of the gastric mucosa using light microscopy, scanning electron microscopy and transmission electron microscopy. We found that 10 mM LPC increased the gastric permeability to both sodium fluorescein and to dextran 3000. Moreover, by transmission electron microscopy, damaged microvillous structures could be seen after LPC treatment. Light microscopy and scanning electron microscopy showed no difference between LPC-treated rats and controls. These findings indicate that LPC, a naturally occurring component in duodenal juice, may damage the gastric mucosa and increase the stomach permeability to larger, potentially pathogenic molecules.