Accurate biodosimetry is needed to estimate radiation doses received in vivo from accidental or unwarranted radiation exposures. We investigated the use of DNA repair foci (e.g. γ-H2AX) at late times after irradiation in vivo as a biodosimeter of initial ionizing radiation dose. Two radiosensitive strains (SCID and BALB/c) and two radioresistant strains (C57BL/6 and C3H/HeJ) were used to quantify γ-H2AX foci in a skin tissue microarray after doses of 1 to 10 Gy at early and late times after irradiation (1 and 7 days). Using a 3D quantitative immunofluorescence microscopy analysis, we observed a dose response for γ-H2AX foci for all strains at 30 min, 24 h and 7 days after irradiation. The numbers of residual foci were significantly different between each of the four strains and reflected the relative radiosensitivity in vivo. In comparing γ-H2AX focus and micronucleus formation after irradiation, we also observed association between the number of micronuclei and number of foci after 1 and 7 days between radiosensitive and radioresistant strains. We conclude that 3D image analysis of γ-H2AX in skin can be used to detect relative radiosensitivity based on late residual γ-H2AX foci. This technique may be a useful biodosimeter to determine dose at times up to 1 week after accidental or catastrophic radiation exposure in vivo.