OBJECTIVE: In a previous article the authors reported associations between nicotine dependence and psychiatric disorders in a community sample of young adults. Increased lifetime rates of major depression and anxiety disorders were found in persons with DSM-III-R nicotine dependence but not in nondependent smokers. The purpose of the present study was to examine the associations of nicotine dependence with four measures of psychologic vulnerability to nonpsychotic psychiatric disorders. METHOD: A randomly chosen group of 1,007 21- to 30-year-old members of a large health maintenance organization were interviewed with the National Institute of Mental Health Diagnostic Interview Schedule, revised for DSM-III-R diagnoses. Self-ratings of neuroticism, negative affect, hopelessness, and general emotional distress were obtained. RESULTS: Nicotine dependence, but not nondependent smoking, was associated with higher scores on all four measures of vulnerability to psychopathology. With one exception the associations between nicotine dependence and these psychologic measures remained significant when the variables current smoking status, history of major depression or anxiety disorders, alcohol and drug use disorders, race, and level of education were controlled; the association of nicotine dependence with general emotional distress was not significant. CONCLUSIONS: Neuroticism and the correlated psychologic vulnerabilities may commonly predispose to nicotine dependence and major depression or anxiety disorders.