In this study we tested the influence of blood flow and the mucoid cap on the penetration of carcinogens to the proliferative cells in the injures rat gastric mucosa. Ten minutes after mucosal exposure to 4.5 mol/liter NaCl, N-[3H]methyl-N'-nitro-N-nitrosoguanidine was instilled intragastrically. Hypertonic saline caused superficial mucosal damage, formation of a mucoid cap, high gastric mucosal blood flow, and a large flux of fluid into the gastric lumen. The mean percentage of S-phase cells labeled with carcinogen (the cell population at risk for N-methyl-N'nitro-N-nitrosoguanidine-induced carcinogenesis) in the antrum and corpus was 0.2 and 0.2, respectively, in the injury control group, 10.1 and 2.0 after removal of the mucoid cap, 1.5 and 9.8 after celiac artery ligation, and 28.2 and 21.9 after removal of the mucoid cap and celiac artery ligation. These results show that both the mucoid cap and gastric mucosal blood flow protect against penetration of carcinogens into the superficially injured gastric mucosa.