Japanese men prefer to smoke cigarettes with charcoal filter tips which are known to selectively reduce certain volatile agents in mainstream smoke (MS). During the past two decades, at least 68% of all cigarettes sold in Japan had charcoal filter tips; in the U.S. such cigarettes have today but 1% of the market. The goal of this study was to evaluate the differences in the levels of major toxic and genotoxic agents in MS of the leading cigarette brands in the U.S. and Japan that account for at least 50% of the respective market. We determined smoke yields of carbon monoxide (CO), volatile aldehydes (VA), hydrogen cyanide (HCN), "tar", nicotine, tobacco-specific N-nitrosamines (TSNA). In addition, benzo(a)pyrene (BaP) and 4-aminobiphenyl (ABP) were determined as surrogates for polynuclear aromatic hydrocarbons (PAH) and aromatic amines, respectively. Although the average weights of the cigarettes are comparable, it is indicated that the leading Japanese 85-mm cigarettes contain less tobacco (0.67 vs 0.73 g/cig.) and burn faster than U.S. brands (7.4 vs 8.3 puffs/cig.). Japanese cigarettes deliver lower yields of total particulate matter (TPM; 14.4 vs 19.1 mg/cig.), BaP (9.3 vs 12.5 ng/cig.), and CO (9.9 vs 13.4 mg/cig.) in MS compared to the leading U.S. brands. The results will be discussed in detail.