The Chinese hamster ovary (CHO) cell mutant EM9 is hypersensitive to ethyl methanesulfonate (EMS) (10-fold) and ionizing radiation (1.8-fold), and it is unable to grow in medium containing chlorodeoxyuridine (CldUrd) under conditions in which 20% of genomic Thy is replaced by chlorouracil during DNA replication (9, 29). EM9 repairs -y-ray and EMS-induced single-strand breaks at a reduced rate and exhibits a 10-fold increase in the occurrence of sister chromatid exchange (SCE) (27,28). The sensitivity of EM9 to alkylating agents is suggestive of a defect in the base excision repair pathway, which involves sequential action by DNA glycosylase, apurinic-apyrimidinic endonuclease, deoxyribose-phosphodiesterase, DNA polymerase, and DNA ligase activities (17). The reduced rate of single-strand break rejoining suggests that the defect in EM9 lies within a postincision step of this pathway. EM9 is phenotypically similar to cells derived from individuals with Bloom's syndrome (BS), a cancer-prone autosomal recessive disorder characterized by high SCEs (10-fold) and sensitivity to alkylating agents (4,14,15 (31). As yet, no specific role has been identified for DNA ligase III (31). Altered DNA ligase activity in BS cells has been observed in several studies, in which it was proposed that the activity of DNA ligase I was affected (5, 6, 33, 34), but no major abnormality in DNA ligase activity was found in the one reported study in which EM9 was examined (7). However,