The effects of intragastric capsaicin and gastric artery ligation on the penetration of the gastric carcinogen N[methyl-3H]-N'-nitro-N-nitrosoguanidine ([3H]MNNG) to proliferative cells were studied in normal and healing rat gastric mucosa. The percentage of S-phase cells labeled with [3H]MNNG in normal corpus mucosa was higher (7.0 +/- 2.0%) after gastric artery ligation than in controls with intact blood flow (2.7 +/- 1.0%) and in animals treated with capsaicin (1.8 +/- 0.5%). Corpus mucosal blood flow was correlated with the percentage of S-phase cells labeled with [3H] MNNG in normal controls and in capsaicin-treated animals. In healing corpus mucosa and in the antrum, capsaicin or gastric artery ligation did not affect carcinogen penetration. We conclude that blood flow protects against penetration of carcinogens to proliferative cells in normal corpus mucosa but not in the antrum. Low mucosal blood flow in the corpus could be a risk factor for initiation of gastric carcinogenesis.