Mining and milling of uranium in Montrose County on the Western Slope of Colorado began in the early 1900s and continued until the early 1980s. To evaluate the possible impact of these activities on the health of communities living on the Colorado Plateau, mortality rates between 1950 and 2000 among Montrose County residents were compared to rates among residents in five similar counties in Colorado. Standardized mortality ratios (SMRs) were computed as the ratio of observed numbers of deaths in Montrose County to the expected numbers of deaths based on mortality rates in the general populations of Colorado and the United States. Relative risks (RRs) were computed as the ratio of the SMRs for Montrose County to the SMRs for the five comparison counties. Between 1950 and 2000, a total of 1,877 cancer deaths occurred in the population residing in Montrose County, compared with 1,903 expected based on general population rates for Colorado (SMR(CO) 0.99). There were 11,837 cancer deaths in the five comparison counties during the same 51-year period compared with 12,135 expected (SMR(CO) 0.98). There was no difference between the total cancer mortality rates in Montrose County and those in the comparison counties (RR = 1.01; 95% CI 0.96-1.06). Except for lung cancer among males (RR = 1.19; 95% CI 1.06-1.33), no statistically significant excesses were seen for any causes of death of a priori interest: cancers of the breast, kidney, liver, bone, or childhood cancer, leukemia, non-Hodgkin lymphoma, renal disease or nonmalignant respiratory disease. Lung cancer among females was decreased (RR = 0.83; 95% CI 0.67-1.02). The absence of elevated mortality rates of cancer in Montrose County over a period of 51 years suggests that the historical milling and mining operations did not adversely affect the health of Montrose County residents. Although descriptive correlation analyses such as this preclude definitive causal inferences, the increased lung cancer mortality seen among males but not females is most likely due to prior occupational exposure to radon and cigarette smoking among underground miners residing in Montrose County, consistent with previous cohort studies of Colorado miners and of residents of the town of Uravan in Montrose County.