To trace the route of vascular protein loss into the stomach lumen during a model protein-losing gastropathy induced by irrigating the stomachs of dogs with dithiothreitol, horseradish peroxidase injected into the vascular system was traced by electron microscopy. T-1824 (Evans blue) was injected into the vascular system, and its presence in the stomach contents indicated the production of a protein-losing gastropathy. Dithiothreitol invariably produced protein-losing gastropathies. Microscopically the damage was observed as dilation of the intercellular space and by vacuole formation in a few surface mucous cells. In control dogs injected with peroxidase, the dense reaction product was always found in the mucosal capillaries, but only rarely in small, restricted areas of the lamina propria. In dithiothreitol-treated animals, the peroxidase reaction product was regularly seen in the blood vessels, the lamina propria, in the dilated and normal undilated intercellular space, and in the gastric lumen. It is concluded that in this acute model protein-losing gastropathy, the major, massive protein loss occurs by an intercellular route.