The sensitivity of scid fibroblasts established from C.B17-scid/scid fetuses to the DNA-damaging agents bleomycin, neocarzinostatin, mechlorethamine, mitomycin C, methyl methanesulfonate, and ultraviolet light, all of which induce different types of DNA damage, was examined. Scid fibroblasts were 2.8-, 3.7-, and 3.0-fold more sensitive to bleomycin, neocarzinostatin, and mechlorethamine, respectively, than wild-type fibroblasts derived from C.B17-+/+ fetuses. These findings indicate that the scid mutation in mice causes defects in repairing both double-strand DNA breaks and DNA cross-links.