The genotoxicity of methylene chloride was determined using sister-chromatid exchange (SCE) and chromosome aberration assays in cultured Chinese hamster ovary (CHO) cells. Methylene chloride caused extensive chromosome aberrations both with and without metabolic activation. However, the results of the SCE assay were negative for methylene chloride. These results agree with previously observed genotoxic effects of methylene chloride in Salmonella typhimurium and Saccharomyces cerevisiae. The fact that methylene chloride causes chromosome aberrations without increasing the SCE level indicates that complete reliance on the induction of SCE as a test system for assessing chromosomal effects is not valid.