Six chloro compounds related to the carcinogen bis(chloro-methyl)ether were tested for carcinogenic activity by subcutaneous injection in ICR/Ha mice and/or as initiating agents in 2-stage carcinogenesis on mouse skin. Two compounds, bis(α-chloroethyl)ether and 2,3-dichloro-tetrahydrofuran, showed tumor-initiating activity. A third compound, chloromethyl methyl ether, included in the subcutaneous injection experiments, had been shown earlier to be an effective initiating agent. All 6 compounds induced subcutaneous sarcomas in mice, but only 2 of the 6, chloromethyl methyl ether and bis(α-chloroethyl)ether, caused significant numbers of sarcomas at the injection site. None of the compounds induced significant incidences of tumors at sites distant from the injection site. Studies on the rate of hydrolysis of these 6 compounds and other related compounds tested earlier showed a good correlation between chemical reactivity and carcinogenicity. Chloromethyl methyl ether and bis(chloromethyl)ether did not affect the Tm and buoyant density of salmon sperm DNA. The unlabeled compounds also did not yield simple isolable products on reaction with purines or DNA under conditions where other direct-acting alkylating carcinogens did.