Fibroblasts derived from patients with hereditary retinoblastoma appear to be more sensitive to the lethal effects of x-rays than do fibroblasts from patients with sporadic retinoblastoma or normal controls. A defect in DNA repair is postulated to account for the high incidence of second tumors in these patients. Retinoblastoma appears to be an interesting model for the study of genetic susceptibility to the development of spontaneous or radiation-induced tumors.