The effects of 450 tobacco ingredients added to tobacco on the forty-four "Hoffmann analytes" in mainstream cigarette smoke have been determined. These analytes are believed by regulatory authorities in the USA and Canada to be relevant to smoking-related diseases. They are based on lists published by D. Hoffmann and co-workers of the American Health Foundation in New York. The ingredients comprised 431 flavours, 1 flavour/solvent, 1 solvent, 7 preservatives, 5 binders, 2 humectants, 2 process aids and 1 filler. The cigarettes containing mixtures of the ingredients were smoked using the standard ISO smoking machine conditions. The levels of the "Hoffmann analytes" in the smoke from the test cigarettes containing the ingredient mixture were compared to those from control cigarettes without the ingredients. In practice, flavouring ingredients are typically added to tobacco that also contains casing ingredients and reconstituted tobacco materials. In order to keep the tobacco mixtures as authentic as possible, three comparisons have been made in this study. These are: (a) control cigarette containing a typical US blended, cased tobacco incorporating reconstituted tobacco versus test cigarettes that had flavouring ingredients added to this tobacco; (b) control cigarette containing tobacco only versus test cigarettes with the tobacco cased and incorporating flavourings; (c) control cigarette containing tobacco only versus test cigarette incorporating additives made in an experimental sheet material. The significances of differences between the test and control cigarettes were determined using both the variability of the data on the specific occasion of the measurement, and also taking into account the long-term variability of the analytical measurements over the one-year period in which analyses were determined in the present study. This long-term variability was determined by measuring the levels of the 44 "Hoffmann analytes" in a reference cigarette on many occasions over the one-year period of this study. The ingredients were added to the experimental cigarettes at or above the maximum levels used commercially by British American Tobacco. The effect of the ingredient mixtures on total particulate matter and carbon monoxide levels in smoke was not significantly different to the control in most cases, and was never more than 10% with any ingredient mixture. It was found that, in most cases, the mixtures of flavouring ingredients (generally added in parts per million levels) had no statistically significant effect on the analyte smoke yields relative to the control cigarette. Occasionally with some of the mixtures, both increases and decreases were observed for some smoke analyte levels relative to the control cigarette. These differences were generally up to about 15% with the mixtures containing flavouring ingredients. The significance of many of the differences was not present when the long-term variability of the analytical methodology was taken into account. For the test cigarettes with ingredient mixtures containing casing ingredients, there were again no significant changes in smoke analyte levels in most cases. Those changes that were observed are as follows. Decreases in smoke levels were observed with some ingredient mixtures for most of the tobacco specific nitrosamines (up to 24%), NO(x), most of the phenols (up to 34%), benzo[a]pyrene, and some of the aromatic amines and miscellaneous organic compounds on the "Hoffmann list". Increases were observed for some test cigarettes in smoke ammonia, HCN, formaldehyde and lead levels (up to 24%). The significance of the ammonia and lead increases was not present when the long-term variability of the analytical methodology was taken into account. The yields of some carbonyl compounds in smoke were increased in one comparison with an additives mixture containing cellulosic components; in particular, formaldehyde was increased by 68%. This was the largest single change seen in any smoke analyte level in this study. These carbonyls are produced from the pyrolysis of cellulosnyls are produced from the pyrolysis of cellulosic and other polysaccharide materials, present in the additives mixture. With this test cigarette, all tobacco specific nitrosamines, phenols, semi-volatile bases, NO(x) and some aromatic amines and miscellaneous organic compounds on the "Hoffmann list" were decreased, by up to 22%. The significance of many of these differences remained even when the long-term variability of the analytical methodology was taken into account. The levels of all other "Hoffmann analytes" in the smoke were not significantly different to those of the control cigarette. With the exception of the determinations of "tar", nicotine and carbon monoxide, there are currently no internationally recognised standard methods for measurement of the other "Hoffmann analytes". Each laboratory uses its own methods and there are large laboratory-to-laboratory variations, as well as variations over time in a given laboratory. Therefore, it is important that in any comparison of smoke analytes amongst different cigarettes, all the analytes should be measured in the same laboratory and at the same time. This was the case in the present study and all the methods have been validated internally.