There is convincing evidence that tobacco smoke produces pharmacologic and toxicologic effects unrelated to its nicotine content. Although nicotine is acknowledged as the major pharmacologically active alkaloid in tobacco that accounts for its continued use, there is much need for further research. It is necessary to systematically compare the complex actions of tobacco with nicotine using different routes of administration, e.g., tobacco smoking produces significant changes in human brain wave patterns. In the present study, topographic EEG methods were used in 14 tobacco smokers and 16 nonsmokers of mixed sex and racial backgrounds. After smoking their favorite cigarette following overnight abstinence from smoking, the tobacco smokers had a shift toward higher EEG frequencies, Delta and theta activity decreased, whereas alpha and beta activity increased. These effects were much less pronounced in nonsmokers who sham smoked an unlit placebo cigarette. Further studies are needed to replicate these findings with nicotine using routes of administration which result in short lasting plasma nicotine boosts similar to those obtained after inhaling tobacco smoke.