This study tested the ability of nicotine to alleviate the tobacco withdrawal syndrome. Signs and symptoms of tobacco withdrawal were measured in 100 smokers who fulfilled DSM-III criteria for tobacco dependence and a past history of tobacco withdrawal. After 2 evenings of baseline measurement, subjects were randomly assigned to receive either nicotine or placebo gum in a double blind manner. Subjects then stopped smoking, chewed gum freely, and returned on the 1st, 2nd, and 4th evenings of abstinence for further measurement. Nicotine reduced the increase in irritability, anxiety, difficulty concentrating, restlessness, impatience, and somatic complaints that subjects reported after cessation. Reductions in these withdrawal symptoms by nicotine were confirmed by ratings of significant others and by subjects' scores on the Profile of Mood States. Nicotine did not reduce the increases in cigarette craving, hunger, eating, insomnia, tremulousness , or supine heart rate after cessation. The effects of nicotine occurred immediately and persisted throughout the study. Although many subjects correctly identified their drug group, the efficacy of the gum was independent of subjects' identifications of drug. The relief of tobacco withdrawal by nicotine gum suggests that the tobacco withdrawal syndrome is caused, in part, by nicotine deprivation.