To test the validity, magnitude, and clinical significance of the signs and symptoms of tobacco withdrawal defined by DSM-III, both observed and reported signs and symptoms were measured in 50 smokers during two days of ad lib smoking and then during the first four days of abstinence. Observer and subject ratings of the DSM-III symptoms of craving for tobacco, irritability, anxiety, difficulty concentrating, and restlessness increased after cessation. In addition, bradycardia, impatience, somatic complaints, insomnia, increased hunger, and increased eating occurred after cessation. The frequency and intensity of these symptoms varied across subjects; however, the average distress from tobacco withdrawal was similar to that observed in psychiatric outpatients. Subjects who had more withdrawal discomfort were more tolerant to the cardiovascular effects of nicotine. Subjects who had more withdrawal discomfort did not have a lower rate of smoking cessation.