Smoking prevalence in the US decreased from 40% in 1965 to less than 29% in 1990; nearly half of all eversmokers have quit. As these people have defected, smoking has become increasingly concentrated in people with cofactors that make them more susceptible and/or render it harder to quit. A possible reason is that the pharmacological properties of nicotine make it suited to managing a variety of behavioral and affective deficits, which may re-emerge upon nicotine abstinence. Abstinence effects have been classified as either "transient", having a brief, biphasic time course, or "offset" -- sustained changes opposite in direction to nicotine agonist effects. This project will test the hypothesis, using adult attention deficit/hyperactivity disorder (ADHD) as a model cofactor, that relevant symptoms that are transient in normal subjects may resemble offset effects in subjects who use nicotine to manage mood or behavioral deficits. The broad, long-term objectives are to elucidate individual differences that contribute to differential nicotine use by exploring the influence of behavioral and effective deficits, as well as the contribution of nicotine dependence, using a series of psychopharmacological strategies; and to lay the groundwork for subsequent behavioral genetics and imaging studies. The specific aims are to carry out a battery of laboratory assessments in men and women smokers with and without adult ADHD. stratified for nicotine dependence, over the course of a 5-day abstinence period, during which daily diaries assessing behavior, mood, sleep, and nicotine abstinence effects will be kept. After 2 and 5 days' abstinence, event related potentials will be tested and a computerized performance test will be administered; on Day 5. An index of potential for developing dependence, will be assessed using a challenge dose of the aerosol. In Study 1, subjects will be tested for emergence of atypical abstinence effects indicative of underlying deficits amenable to normalization by nicotine. In Study 2, subjects will be randomly assigned to methylphenidate or placebo to determine the impact of methylphenidate on study variables. The health relevance is that conditions like adult ADHD are public health problems in their own right, taking an enormous toll in terms of lost productivity and diminished quality of life; to the extent that they increase likelihood of smoking, the most important preventable cause of morbidity and mortality, the health consequences are magnified. Findings from this study increase our understanding of mechanisms linking cofactors with nicotine use, facilitating development of interventions that reduce risk of treatment failure.