Aspirin administration results in gastric mucosal damage. Although the pathogenesis of these lesions remains unclear, in animals it appears that increased vascular permeability precedes development of grossly visible lesions. We examined the effect of aspirin administration on gastric vascular permeability in eight healthy subjects. We used gastric accumulation of Evan's blue dye (which is bound to albumin) as a marker of vascular integrity and assessed gastric accumulation of Evan's blue, blood, and DNA during serial 10-min washes. Both bleeding and Evan's blue in the gastric washings increased with time after administration of aspirin in an acid solution (P less than 0.01). Evan's blue increased from a median value of 8 micrograms/10 min to 24.5 micrograms/10 min period after 60 min of aspirin administration. By 20 min after aspirin administration, the accumulation of Evan's blue in the gastric wash was significantly greater than the initial aspirin period (P less than 0.05). Blood loss increased from 147 to 650 micrograms Hgb/10-min period. The increase in bleeding rate did not become significant until 40 min after the first aspirin dose. Our study showed that aspirin-induced gastric mucosal damage can be detected by assessing accumulation of Evan's blue in the gastric contents after aspirin administration. Studies in which various doses of aspirin or other agents are administered will be required to confirm whether the increased vascular permeability actually precedes bleeding in man. Measurement of Evan's blue dye in the gastric contents appears to provide a qualitative (and possibly quantitative) and sensitive early index of gastric mucosal injury.