Whereas members of the Navajo Nation are at high risk for diabetes mellitus, there are no recent published estimates of the burden of end-stage renal disease (ESRD), an important sequela of diabetes, on the Navajo Nation, a 16 million acre area in Arizona, New Mexico, and Utah with more than 200 000 tribal members. We used data from the US Renal Data System to estimate the prevalence and incidence of ESRD among Native American adults (>/=18 years) living on the Navajo Nation. For comparison, we estimated the prevalence and incidence of ESRD among all adults in the US, all Native American adults in the US, and Native American adults living in Arizona, New Mexico, Utah, and Colorado excluding those living on the Navajo Nation. The age-adjusted prevalence of ESRD in the Native American adults on the Navajo Nation was 0.63%, which was higher than in the US adults (0.19%, P<0.0001) and among the Native American adults in the US (0.36%, P<0.0001), but lower than among the other Native American adults in the Southwest (0.89%, P<0.0001). The age-adjusted incidence of ESRD in the Native American adults on the Navajo Nation was 0.11%, which was also higher than in the US adults (0.045%, P<0.0001) and among the Native American adults in the US (0.073%, P<0.0009), but lower than among the other Native American adults in the Southwest (0.17%, P<0.0003). The reasons behind these disparities merit further study.