The sister chromatid exchange (SCE) test system using human peripheral lymphocytes is proposed as a valuable tool for the cytogenetic monitoring of exposure to potential chemical mutagens in the occupational environment. We examined the SCE frequencies in organic solvent-exposed workers and reviewed the effects of occupational and environmental chemicals on SCE frequencies. The results obtained in these exposed populations are rather contradictory, which may be related to confounding factors, such as personal life style (smoking, drinking, and drugs) of the examinees, tissue culture conditions and the number of subjects examined. We discussed some practical problems for exposure estimation and sample size determination and are led to the following conclusions. 1) The possible combined effects of potential mutagens and cigarette smoking should be taken into consideration when using the SCE test system. 2) Cell cycle kinetic analysis by differential chromatid staining would provide valuable information as a biological indicator for the monitoring of the workers exposed to xenobiotics. 3) By appropriately setting the number of examinees, monitoring would become more efficient in detecting an increased SCE frequency in the exposed populations. Further studies are also required to enhance the sensitivity of the SCE test system for monitoring purposes.