Reactive oxygen species (ROS)-induced skin erythema was produced by injection of xanthine oxidase (XOD) and hypoxanthine (HPX), an R05-producing system, into guinea pig skin. The clinical course of the erythema was examined in relationship to the age of the animal as well as to superoxide dismutase (SOD) activity of the skin, The R05-induced skin erythema reached a peak 24 hr after injection of XOD and HPX macroscopically and histologicallywith the reduction of skin SOD activity, and the severityof erythema was age-dependent. The increased severityof the skin erythema with age was related to the reduction of the skin SOD activities after XOD plus HPX injection. This skin erythema will provide a good model for the investigation of oxidative tissue injuries observed in several skin disorders.