Effect of free radicals on microvascular dimensions was studied in anesthetized cat intestinal mesentery. Generation of free radicals by xanthine oxidase, acting on endogenous substrates (e.g., xanthine, hypoxanthine), produced sustained vasodilation at pH 7.4 or at pH 6.6. These effects were reversed by superoxide dismutase (SOD), a superoxide radical (.O2-) scavenger, at pH 7.4, and by SOD plus hydroxyl radical (.OH) scavenger d-mannitol at pH 6.6. These findings suggest that the sustained vasodilation is caused by .O2- and by .OH derived from .O2- at low pH.