Chronic low-dose exposure to solvents has been associated in epidemiologic studies with chronic neurotoxicity, but the evidence is not consistent. Styrene causes acute disturbances in the central and peripheral nervous systems. To determine if exposure to styrene may contribute to chronic diseases of the central nervous system, the authors examined mortality from nervous system diseases, mental disorders, and suicide in relation to styrene exposure in an international historical cohort study. The cohort involved 35,443 workers employed during 1945-1991 in the reinforced plastics industry, where high exposures to styrene occur. Indicators of exposure were reconstructed through job histories and environmental and biologic monitoring data. Poisson regression was used for internal comparisons. Mortality from diseases of the central nervous system (27 deaths) increased with time since first exposure, duration of exposure, average level of exposure, and cumulative exposure to styrene. A quadratic model described best the dose-response shape for cumulative exposure and duration of exposure with the highest risks at around 300 ppm-years and 5 years, respectively, and a subsequent decrease in risk in the highest exposure categories. Mortality from epilepsy increased monotonically with all styrene exposure indicators, while associations for degenerative diseases of the central nervous system were generally weaker. Mortality from mental disorders and suicide decreased with increasing duration of exposure and cumulative exposure, while there was no trend with time since first exposure and average exposure to styrene. These findings suggest that, in addition to the known acute effects, exposure to styrene may contribute to chronic diseases of the central nervous system.