Our previous study suggested that histamine might enhance the increase of ornithine decarboxylase activity in injured intestinal mucosa. To test this hypothesis, we measured histamine content in mesenteric lymph and ornithine decarboxylase activity in intestinal mucosa after ischemia-reperfusion in the rat. We examined the effect of alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, on ornithine decarboxylase activity after ischemia-reperfusion and compared this with its effect on the rat after refeeding. Ischemia-reperfusion was performed by 15-min occlusion of the superior mesenteric artery. After ischemia-reperfusion, histamine content in mesenteric lymph increased, and this increase was completely suppressed by alpha-fluoromethylhistidine pretreatment. In contrast to ischemia-reperfusion, histamine content in mesenteric lymph did not change after refeeding. Ornithine decarboxylase activity increased markedly 3 and 6 hr after ischemia-reperfusion and refeeding, whereas alpha-fluoromethylhistidine attenuated the increase in ornithine decarboxylase activity only in the ischemia-reperfusion group. These results indicate that increase in histamine synthesis in the intestinal mucosa plays an important role in the increase of ornithine decarboxylase activity after ischemia-reperfusion but that histamine is not related to the increase in ornithine decarboxylase activity after refeeding.