This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this study is to assess alterations in cerebral activation patterns resulting from cigarette smoking and withdrawal from chronic nicotine self-administration. Functional MRI will be used to measure the ability of cognitive and motor tasks to increase cerebral activity dependent upon smoking status, withdrawal time, and intensity of withdrawal symptoms. 110 chronic cigarette smokers and 40 age- and education-matched controls (18-50 years) will be screened by telephone, then visit the GCRC for informed consent, history, and physical exam, and structured interview and questionnaires to permit scoring for nicotine dependence. Exhaled CO will be measured. Subjects will then undergo whole body structural and functional MRI scanning (3T), during which task activation and performance testing will be performed. Subjects in SA 1 (differences between chronic smokers and nonsmokers in task activation) will be scanned once, 5 times in SA 2 (altered task activation with cessation), and 4 times in SA 3. Subjects in SA 3 (role of nicotine in the withdrawal syndrome) will receive IV and/or patch nicotine replacement. GCRC nursing support is requested to obtain and process blood and urine samples, assist with consenting, and place IV lines. GCRC nurses are also needed to assist with drug run-up procedures on the IV nicotine subjects. GCRC Biostatistics is needed for data analysis, the fMRI Core for scanning analysis. GCRC support is also requested for scanning fees, CBC and AST testing, and urine drug triage, pregnancy testing, and cotidine testing.