In April 2008, the Arctic Investigations Program (AIP) of CDC was informed by the Alaska Department of Health and Social Services (DHSS) of a large number of Alaska Native (AN) children living in a remote region of Alaska who required full mouth dental rehabilitations (FMDRs), including extractions and/or restorations of multiple carious teeth performed under general anesthesia. In this remote region, approximately 400 FMDRs were performed in AN children aged <6 years in 2007; the region has approximately 600 births per year. Dental caries can cause pain, which can affect children's normal growth and development. AIP and Alaska DHSS conducted an investigation of dental caries and associated risk factors among children in the remote region. A convenience sample of children aged 4-15 years in five villages (two with fluoridated water and three without) was examined to estimate dental caries prevalence and severity. Risk factor information was obtained by interviewing parents. Among children aged 4-5 years and 12-15 years who were evaluated, 87% and 91%, respectively, had dental caries, compared with 35% and 51% of U.S. children in those age groups. Among children from the Alaska villages, those aged 4-5 years had a mean of 7.3 dental caries, and those aged 12-15 years had a mean of 5.0, compared with 1.6 and 1.8 dental caries in same-aged U.S. children. Of the multiple factors assessed, lack of water fluoridation and soda pop consumption were significantly associated with dental caries severity. Collaborations between tribal, state, and federal agencies to provide effective preventive interventions, such as water fluoridation of villages with suitable water systems and provision of fluoride varnishes, should be encouraged.