The effects of aspirin on the canine gastric mucosal barrier were examined using the freeze-fracture and extracellular tracer techniques. Aspirin treatment (3, 20, or 40 min) resulted in alterations in tight junction complex morphology and permeability. Discontinuities in the apical occluding complex, hyperplastic tight junctions (extensions of the apical tight junction strands radiating over the lateral plasma membrane), and a variability in the number of strands (1-20) comprising the complex were observed. A concurrent increase in lanthanum permeability between nonnecrotic surface mucous epithelial cells was also demonstrated. The results of these experiments may suggest that aspirin-induced impairment of the tight junction complexes between viable gastric mucosal epithelial cells may be a major contributing factor in the etiology of stomach disorders.