Angiogenesis in tumors is influenced by several factors which in turn are associated with chemoresistance or radioresistance. Moreover, the tumors of smokers are known to be relatively resistant to chemotherapy. This investigation attempts to determine whether or not a relationship exists between cigarette smoking and angiogenesis in lung cancer. Tumor samples from 14 non-smokers and 14 heavy cigarette smokers were selected for this study. The populations were matched for age, sex and tumor stage. Resistance to doxorubicin, microvessel density, the expression of vascular endothelial growth factor (VEGF) and thrombospondin (TSP) were analyzed in both populations. Tumors of smokers were more frequently resistant to doxorubicin in vitro, had lower vessel counts and a reduced expression of VEGF compared to tumors of nonsmokers. In contrast, TSP was significantly increased in the tumors of smokers. These data show that angiogenesis in lung tumors is linked to a patient's smoking habits.