Sidestream cigarette smoke, the major componentof environmental tobacco smoke, is a complex and reactiveaerosol. The particulate matter (PM) in sidestream smoke isone of the carriers of chemical constituents. However, particlesize-dependent toxicological effects of PM are poorly under-stood. In this study, we evaluated the relationship between thePM size and in vitro cytotoxicity and mutagenicity of side-stream cigarette smoke. A NanoMoudi-II™125Awas used tocollect PM samples ranging from 10 nm to 10 μm. Thein vitro toxicity of PM was evaluated using a neutral red cy-totoxicity assay and Salmonella mutagenicity assay. The re-sults showed that the cytotoxicity and mutagenicity of PMlarger than 1 μm was significantly lower than PM sized10 nm–1 μm. Furthermore, there was a noticeable trend thatthe smaller the size of the PM of sidestream cigarette smoke,the greater the toxicity. This study suggests that the toxicity ofPM in sidestream cigarette smoke is size-dependent.