To explore the tobacco industry's interest and intentions driving its nicotine analogue research. Review of internal tobacco industry documents regarding nicotine analogues released as part of the Master Settlement Agreement between the tobacco industry and US state governments in 1998. The tobacco industry investigated nicotine analogues extensively. Four principal areas of interest are evident. First, research on tobacco products was directed towards greater understanding of nicotine pharmacology, how to screen for potential analogues and how to separate the central and peripheral effects of nicotine. Secondly, interest lay in the potential for analogues to replace nicotine in order to create more 'desirable' products and to circumvent anticipated nicotine regulation. Thirdly, interest lay in potential pharmaceutical applications for analogues such as treatments for neurological disorders. Finally, there was interest in the public relations potential of the therapeutic potential of analogues to reduce the demonization of nicotine, by allowing the industry to point to its beneficial uses. With tobacco product and nicotine regulation being increasingly advocated in tobacco control it is important to understand the industry's interests in the potential role of nicotine analogues. Initial interest included using analogues as a means to circumvent regulation, but evidence suggests these plans were discarded due to fear that this may have instigated regulation of tobacco products. Nicotine analogue research has led to potential therapeutic uses for Alzheimer's and Parkinson's diseases and alarmingly for the industry, to a potential vaccine to prevent nicotine addiction. Tobacco manufacturers should be obliged to declare all additives being used in tobacco products. Regulatory bodies should be aware that that there is a distinct possibility that the industry has discovered ways to circumvent future regulation of nicotine through the utilization of nicotine analogues. Any regulatory drafting should broaden the definition of nicotine in order to incorporate analogues into the scope of pharmacologically active substances being regulated.