Published reports about skin reactions to radiotherapy, especially among breast-cancer patients, suggest that there are interindividual differences in the normal tissue response, and genetic factors are thought to be involved in this variation. An analysis of murine strain differences may reveal the mechanism of genetic factors in the extent of normal tissue damage from irradiation for several endpoints. The variation in the radiation susceptibility was observed when the skin of mice from strains A/J, C3H/HeMs, C57BL/6J, C.B.17/Icr-scid and C3H-scid was irradiated with a single dose ranging from 10 to 60 Gy, using Cs-137 gamma rays. The active skin reaction of A/J mice lasted for months. C3H/HeMs mice showed dose-dependent skin damage, and consequently recovered to a state of mild damage within 40 days after local irradiation. The time course of the response in C57BL/6J mice was shorter than in A/J mice. The 2 strains of scid mice exhibited severe damage after irradiation at any dose from 20 to 50 Gy, and did not show any dose dependency. The variation between murine strains in macroscopic and histopathological changes in skin during the progression and resolution of damage caused by irradiation suggests an inter-strain variation in the expression of genes involved in injury, apoptosis, repair, and remodeling.