BACKGROUND: As the population and demand for safe drinking water from domestic wells increase, it is important to examine water quality and contaminant occurrence. A national assessment in 2006 by the U.S. Geological Survey reported findings for 55 volatile organic compounds (VOCs) based on 2,401 domestic wells sampled during 1985-2002. OBJECTIVES: We examined the occurrence of individual and multiple VOCs and assessed the potential human-health relevance of VOC concentrations. We also identified hydrogeologic and anthropogenic variables that influence the probability of VOC occurrence. METHODS: The domestic well samples were collected at the wellhead before treatment of water and analyzed for 55 VOCs. Results were used to examine VOC occurrence and identify associations of multiple explanatory variables using logistic regression analyses. We used a screening-level assessment to compare VOC concentrations to U.S. Environmental Protection Agency maximum contaminant levels (MCLs) and health-based screening levels. RESULTS: We detected VOCs in 65% of the samples; about one-half of these samples contained VOC mixtures. Frequently detected VOCs included chloroform, toluene, 1,2,4-trimethylbenzene, and perchloroethene. VOC concentrations generally were < 1 microg/L. One or more VOC concentrations were greater than MCLs in 1.2% of samples, including dibromochloropropane, 1,2-dichloropropane, and ethylene dibromide (fumigants); perchloroethene and trichloroethene (solvents); and 1,1-dichloroethene (organic synthesis compound). CONCLUSIONS: Drinking water supplied by domestic wells is vulnerable to low-level VOC contamination. About 1% of samples had concentrations of potential human-health concern. Identifying factors associated with VOC occurrence may aid in understanding the sources, transport, and fate of VOCs in groundwater.