Nicotine withdrawal is typically associated with negative changes in mood and performance, which often lead to relapse. We tested whether an oral 0.3-mg dose of melatonin administered 3.5 h after the nicotine withdrawal, and increasing circulating melatonin concentrations within the physiological range, affects the symptoms of acute 10-h (0800-1800 h) nicotine withdrawal in regular smokers. Self-reported ratings of mood, sleepiness, and cigarette craving were assessed hourly, using 17 visual analog scales (VAS). Computerized Four-Choice Reaction Time (FCRT) and Simple Auditory Reaction Time (SART) tests were used to assess performance every 2 h. Saliva samples were collected hourly, and salivary melatonin levels were measured using supersensitive radioimmunoassay. Compared with the placebo, melatonin treatment significantly reduced self-ratings of "anxious," "restless," "tense," "irritable," "angry," "depressed, " "impatient," and "craving for cigarettes." Melatonin treatment did not significantly change the responses on the performance tests used. These data suggest that melatonin can help to counteract the acute effects of smoking cessation on mood.