Ethylene oxide (EO) presents a major challenge in the area of risk assessment. EO reactivity is but one feature of the challenging problem of hazard evaluation of EO. The different circumstances of production and use of EO have been reflected in different patterns of exposure of the workforce. The positive evidence of genotoxicity of EO in lower organisms, and increased Sister-chromatid exchange in peripheral lymphocytes of workers exposed to EO, will be more amenable to interpretation when the new techniques now becoming available permit measurement of EO-DNA adducts in people. EO, the first member of the homologous series of monofunctional aliphatic epoxides is a highly reactive chemical agent possessing a strained ring structure, a property that also finds expression in the biological reactivity of EO. The animal carcinogenicity data illustrate such biological considerations. In view of the high and variable levels of spontaneously occurring mononuclear cell leukemia in Fischer 344 rats, the experimental results lend themselves to different interpretations.