The Friend virus-infected murine erythroleukemia cell can be induced to differentiate along erythroid cells in culture with various compounds, including dimethyl sulfoxide. DNA from murine erythroleukemia cells cultured with dimethyl sulfoxide shows a decrease in sedimentation rate in alkaline sucrose gradients after alkali lysis of the cells. These changes can be detected as early as 27 hr after the beginning of culture. Similar results are observed with DNA of the cells cultured with other inducers, butyric acid and dimethylacetamide, but not with DNA from a variant cell line resistant to induction with dimethyl sulfoxide. Ultraviolet irradiation, which is known to cause similar changes in the sedimentation rate of DNA in alkaline sucrose gradients, induces differentiation of the murine erythroleukemia cells. These studies suggest that alterations in DNA may be related to events involved in the induction of differentiation of murine erythroleukemia cells by dimethyl sulfoxide.