OBJECTIVE: The biopersistence of refractory ceramic fiber (RCF) in human lung tissue is unknown and may contribute to an association between cumulative fiber exposure and radiographic changes. METHODS: Lung tissue fiber was analyzed for a case series of 10 RCF workers and a 20-year longitudinal chest radiograph study of 1323 workers was conducted. RESULTS: Within lung tissue, RCF comprised 14% to 100% of fibers 5 μm or more in length and was identified up to 20 years after RCF employment. Among workers with no reported asbestos exposure, cumulative exposure of more than 63 to 110 and more than 110 fiber-months/cm was associated with radiographic pleural changes of 8.5% (odds ratio, 7.2; 95% confidence interval, 1.4 to 36.8) and 11.6% (odds ratio, 10.3; 95% confidence interval, 2.1 to 49.9), respectively. CONCLUSIONS: Refractory ceramic fiber can persist in human lung tissue for up to 20 years and may contribute to the significant association between cumulative fiber exposure and radiographic pleural changes.