A study of the effects of cigarette smoking and solvent exposure on sister chromatid exchange (SCE) frequency in peripheral lymphocytes of painters was conducted. The cohort consisted of 117 members of local unions of the International Brotherhood of Painters and Allied Tradesmen in two United States cities. The final group of 106 analyzable subjects had a mean age of 42.6 years and included only two females. Twenty one subjects reported little or no occupational solvent exposure (unexposed subjects). Information on occupational and medical histories, smoking habits, coffee and alcohol consumption, detailed data on solvent exposures, and demographic data were obtained in an interviewer administered questionnaire. Solvent exposures were estimated from the questionnaire data. Peripheral venous blood samples were collected, the lymphocytes were isolated, and assayed for SCEs. All slides were scored by one reader, and 30 randomly chosen samples were also scored by a second reader. Coffee and alcohol intake and age did not significantly affect the incidence of SCEs. There was no significant difference in the SCE frequency between unexposed subjects and painters. A significant elevation of SCE frequency associated with current smoking was found in both the exposed and unexposed subjects. In the painters, lifetime solvent exposure, exposure during the year preceding venipuncture, and cumulative years of exposure were not associated with an increase in SCE frequency. The authors conclude that chronic solvent exposure in painters is not associated with an increased frequency of SCEs in peripheral lymphocytes. Further research should be conducted to investigate the genotoxic effects of acute occupational exposure to solvents.