Perfluorooctanoic acid (PFOA) is persistent in the human body; the general population has serum levels of approximately 4 ng/mL. It causes tumors of the liver, pancreas, and testicles in rodents. The authors studied the mortality of 5,791 workers exposed to PFOA at a DuPont chemical plant in West Virginia, using a newly developed job exposure matrix based on serum data for 1,308 workers from 1979-2004. The estimated average serum PFOA level was 350 ng/mL. The authors used 2 referent groups: other DuPont workers in the region and the US population. In comparison with other DuPont workers, cause-specific mortality was elevated for mesothelioma (standardized mortality ratio (SMR) = 2.85, 95% confidence interval (CI): 1.05, 6.20), diabetes mellitus (SMR = 1.90, 95% CI: 1.35, 2.61), and chronic renal disease (SMR = 3.11, 95% CI: 1.66, 5.32). Significant positive exposure-response trends occurred for both malignant and nonmalignant renal disease (12 and 13 deaths, respectively). PFOA is concentrated in the kidneys of rodents, and there are prior findings of elevated kidney cancer in this cohort. Multiple-cause mortality analyses tended to support the results of underlying-cause analyses. No exposure-response trend was seen for diabetes or heart disease mortality. In conclusion, the authors found evidence of positive exposure-response trends for malignant and nonmalignant renal disease. These results were limited by small numbers and restriction to mortality data, which are of limited relevance for several nonfatal outcomes of a priori interest.