Numerous approaches have been taken to test the biological activity of cigarette smoke in vitro. The various experimental approaches involve strategies leading to different exposure situations for the cells. From the point of view of smoke testing, the most important aspects are (1) the condition of the cigarette smoke and (2) the contact of the cells with the gas phase and the particulate matter. Since fresh cigarette smoke contains thousands of different compounds and many short lived radicals, any physical or chemical conditioning as well as ageing will clearly change its composition. On the other hand, the cultivation of cells requires certain conditions for maintaining cellular viability (temperature, humidity, pH, nutrition). Hence, any experimental set-up for cell exposure to gases and complex mixtures in vitro has to resolve conflicts between requirements for maintaining the physical and chemical properties of the test atmosphere and requirements for maintaining cellular viability. In the case of complex mixtures with particulate phases, this scenery is even more complex due to the deposition of particles on the cellular surface, leading to specific requirements for the exposure conditions. Against this background, a newly designed exposure set-up is presented which involves the direct exposure of human lung cells to native, unmodified cigarette mainstream smoke. The system consists of a smoking machine, a dilution device for the smoke, analytical devices for online monitoring and a specially adapted exposure module based on the Cultex cell cultivation system (Pat. No. DE 19801763/PCT/EP99/00295) equipped with a gas-exposure top. Due to the special construction of the exposure device and optimised exposure conditions this set-up allows human lung cells to be exposed to freshly generated cigarette mainstream smoke under preservation of cellular viability. Furthermore, experiments demonstrated that particles are deposited on the cells and that the smoke induced dose-dependent cellular effects.