Abstract: To investigate the emission and toxicology characteristics in mainstream smoke of cigarettes with different circumferences, the routine smoke indexes, the priority toxicant H index and in vitro toxicology of mainstream smoke of research cigarettes with three different circumferences of the same tobacco blend were analyzed under ISO and Health Canada Intensive (HCI) smoking regimes. The puff-by-puff release characteristics of routine smoke indexes of mainstream cigarette smoke were studied as well. The results showed that:1) Under ISO smoking regime, the mainstream smoke release from the cigarette with medium circumference had the lowest routine smoke indexes and H index per unit nicotine yield. Under HCI smoking regime, with the decrease of cigarette circumference, the H index per unit nicotine yield decreased. 2)Under the different smoking regimes, with the decrease of cigarette circumference, the in vitro cytotoxicity of total particulate matters decreased generally, however no obvious difference was observed in genotoxicity and mutagenicity. 3)For the cigarettes with the different circumferences, the puff-by-puff releases of routine smoke indexes of mainstream cigarette smoke generally increased with the puff number.