ABSTRACT This study evaluated unique exposures and their relationship to brain cancer mortality in employees of a specialty chemical research facility. Following an exposure assessment that concerned compounds distinct to this facility, the authors conducted a cohort mortality study of 5,284 workers to assess mortality in reference to the general population and a nested case-control study to evaluate brain cancer risk associated with specific jobs and unique chemical exposures. Four hundred eighty-six deaths, including 14 brain cancer deaths, were identified. Overall mortality was lower than expected. Brain cancer mortality was elevated (standardized mortality ratio [SMR] = 2.02, 95% confidence interval [CI] = 1.11-3.40). Exposures to 5 specific chemical categories were assessed. Exploration of work history and the specific chemical exposures did not explain the brain cancer cases. No clear occupational etiology was identified.