Abstract: In order to investigate the synergistic effect of smoking and radon in the absence of confounding factors, an in vitro study was carried out to compare chromosome aberrations in blood lymphocytes of smokers and non-smokers. Blood samples were exposed to different concentrations of radon ranging from 0 to 35643.223 kBq m-3 corresponding to mean doses of 2.9±0.27 mGy (non smokers) and 2.7±0.25 mGy (smokers) using a simple, portable irradiation assembly. Chromosome aberrations in giemsa stained first division metaphase preparations were scored. The results show that compared to nonsmokers there is a significant increase in radon-induced dicentrics, acentric fragments and chromatid breaks in smoker cells. The study implies that chromosomes in smoker cells are more unstable to radon exposure and thus the effect acts synergistically to the risk of cancer.