There is limited information on the prevalence of the potent mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in U.S. water supplies. We measured MX concentrations and mutagenic activity in tap water samples from 36 surface water systems throughout Massachusetts. We found MX levels much higher (up to 80 ng/L) than previously reported in the United States. We also evaluated the role of water treatment on mutagenic activity and disinfection by-product formation. After adjusting for other covariates, chloramination and filtration were the most important treatment options for reducing mutagenic activity and disinfection by-product formation. Multiple chlorine application (before and after filtration) was associated with increased mutagenicity. Chlorine dose, pH, and total organic carbon were also associated with mutagenicity, MX, and total trihalomethane (TTHM) concentration. Seasonal variation was evident for MX and mutagenic activity, with higher levels occurring in the spring compared to the fall. In contrast, TTHM concentrations were greater in the fall.