DESCRIPTION: (Applicant's Abstract) The addiction to use of tobacco products is one of the most common and most destructive addictions in the world today. It is estimated that nearly half of the world population smokes cigarettes. Few of the biological markers commonly used to monitor smoking cessation provide information on long term use of tobacco products, nor any type of prediction of success in quitting the smoking habit. We have shown that nicotinic acetylcholine receptors, the receptors responding to nicotine in cigarettes, are increased in postmortem brain of subjects who were smokers in life, but decline to near control values in subjects who had ceased to smoke for varying periods before death. Nicotinic receptors are also expressed in the white cells of peripheral blood, which is easy to obtain in a clinical setting. Peripheral blood neutrophils have a similar regulatory response to use of tobacco products as is seen in brain. The proposed studies would develop the assay for nicotinic receptor levels in peripheral blood as a biological marker for monitoring smoking cessation. We will 1) optimize the nicotinic receptor binding assay for peripheral blood neutrophils, 2) determine the range of nicotinic receptor expression in blood neutrophils in never-smokers and in subjects with variable smoking histories, and 3) evaluate the utility of this assay in an actual smoking cessation program.