We describe the epidemiology of nicotine dependence and Us association with other substance use and psychiatric disorders. Data came from a random sample of young adults, 21–30 years of age, in the Detroit, Michigan metropolitan area. The NIMH Diagnostic Interview Schedule was used to ascertain DSM-III-R disorders. Lifetime prevalence of nicotine dependence was 20%. Higher rates were observed in whites, persons with low education and persons who were separated or divorced. Males and females with nicotine dependence had significantly increased odds for alcohol and illicit drug disorders, major depression and one or more anxiety disorder, as compared to non-dependent smokers and non-smokers combined. Among smokers, lifetime prevalence of illicit drug disorders other than marijuana alone, major depression and any anxiety disorder were significantly higher in dependent than non-dependent people. Major depression was associated specifically with nicotine dependence, an association explained in part by neuroticism. This finding suggests that the personality trait of neuroticism might constitute a common predisposition for major depression and nicotine dependence.