The purpose of this grant is to determine the interactions between stress, smoking, and nicotine and whether public speaking, as a representative stressor, will increase smoking nicotine seeking, and influence blood nicotine levels. Three hypotheses will be tested. The first proposes that increased smoking during stress represents increased nicotine seeking. The second predicts that stress causes increased nicotine depletion secondary to acidification of urine and consequent increased excretion of nicotine. The third investigates whether smokers under stress seek to restore blood levels of nicotine to baseline levels or whether they seek reinforcement from increased levels of nicotine. The outcome of the experiments will determine how the investigation of the underlying physiological and pharmacological mechanisms of the stress nicotine interaction will proceed.