This paper presents an overview of a series of studies designed to assess the influence of 482 tobacco ingredients on cigarettes smoke chemistry and toxicity. The studies are pyrolysis of the ingredients, and influence of the ingredients on smoke "Hoffmann analytes", in vitro genotoxicity and cytotoxicity of smoke condensate and inhalation toxicity of smoke. A pyrolysis technique has been developed that mimics the combustion conditions inside a burning cigarette. The results from a subset of 291 single-substance ingredients indicate that almost a third would transfer out of the cigarette burning zone at least 99% intact, and almost two thirds would transfer at least 95% intact. Of the ingredients that underwent some degree of pyrolysis, a few "Hoffmann analytes" were detected amongst the pyrolysis products of 19 ingredients. Taking into account likely use levels, their maximum pyrolysis levels were generally small and often insignificant compared to the levels typically present in smoke. When the 482 ingredients were added to tobacco in various mixtures, many of the ingredient mixtures produced no significant effect on the levels of many of the "Hoffmann analytes" in smoke, while some produced increases or decreases relative to the relevant control cigarettes. The study has concentrated on the increases. Many of the differences were found to be not significant when the long term variability of the analytical methodology was taken into account.The activity of smoke condensate from cigarettes containing tobacco ingredients has been determined using three in vitro bioassays, two for genotoxicity and one for cytotoxicity. These were the Ames test, the mammalian cell micronucleus assay, and the neutral red uptake cytotoxicity assay. Within the sensitivity and specificity of these bioassays, the specific activity of the cigarette smoke condensate was not increased by the addition of ingredients to the cigarette. The effects of ingredients on the inhalation toxicity of the smoke will also be discussed.