Studies of overlapping cohorts in the United States have shown an excess mortality from brain cancer in vinyl chloride (VC)-exposed workers. One plant located in Louisville, Kentucky, is included in many of these studies. We separated this plant from the large US cohort and re-analyzed the mortality experience. Louisville experienced significantly elevated liver (standardized mortality analyses [SMR] = 400) and brain cancer (SMR = 229) mortality. Liver cancer mortality remained significantly elevated (SMR = 344) in the remaining cohort; however, brain cancer mortality was markedly reduced (SMR = 112) when Louisville was removed. In contrast with liver cancer, a preliminary review of work assignments did not suggest that the brain cancer excess was related to VC exposure. The Louisville brain cancer cluster has had a significant impact on the reported literature. Although unrelated to VC, the cause of this cluster remains uncertain.