Cigarette smoking is commonly linked to the consumption of caffeinated beverages, especially coffee. Epidemiological studies suggest strong correlations between number of cigarettes smoked and quantity of coffee consumed daily. Furthermore, the act of coffee-drinking can be a strong stimulus for smoking in many individuals. The long-term objective of this research program is to determine whether the association of coffee or caffeine consumption with smoking contributes significantly to the adverse health consequences or addictive potential of smoking. The application considers three different areas in which coffee drinking could contribute to the risks of smoking. First, caffeine consumption could potentiate the sympathomimetic effects of nicotine and increase their pathogenicity. Caffeine is known to potentiate other sympathetically mediated responses. A laboratory study will examine the dose-related effects of caffeine pretreatment on sympathetically mediated cardiovascular and neuroendocrine responses to a controlled dose of nicotine in cigarette smoke. Second, the consumption of caffeine or coffee could affect a smoker's ad lib intake of cigarette smoke and nicotine through pharmacological or behavioral mechanisms. A laboratory study will examine the separate and combined effects of caffeine administration and coffee-drinking behaviors on short-term smoking behavior and nicotine intake. A related study will examine the effects of caffeinated vs. dicaffeinated coffee consumption on ad lib smoke and nicotine intake during week-long periods of normal activity. Third, caffeine consumption could make smoking cessation more difficult and increase the likelihood of relapse by adding to or intensifying the symptoms of tobacco abstinence or by altering the cognitive and performance deficits that appear during abstinence. One study will examine tbe effects of caffeinated vs. decaffeinated coffee on withdrawal symptoms and craving during 4-day periods of experimental smoking abstinence. A related laboratory study will examine dose-related caffeine effects on the performance decrements associated with acute smoking deprivation. Each of the five studies will also explore potential racial or ethnic differences in caffeine/coffee effects and smoking behaviors by the inclusion and direct comparison of groups of White and Black subjects in each protocol. Together, these five proposed studies should provide new insights into cigarette smoking behavior and its health consequences. Furthermore, an understanding of the effects of caffeine and coffee drinking on smoking behavior should yield practical suggestions that will enhance clinical efforts directed at smoking cessation.