To determine whether nicotine dependence, classified by level of severity, was associated with other substance dependence, major depression, and anxiety disorders, we studied a random sample of 1007 young adults in the Detroit (Mich) area using the National Institute of Mental Health Diagnostic Interview Schedule, revised according to DSM-III-R. The systematic coverage of DSM-III-R criteria of nicotine dependence provides an unprecedented opportunity to separate persons with nicotine dependence from the larger class of persons with a history of smoking and to examine the prevalence of psychiatric disorders among persons with nicotine dependence and among nondependent smokers. The lifetime prevalence of nicotine dependence was 20%. Nicotine dependence was associated with alcohol, cannabis, and cocaine dependence. Controlling for the effects of other substance dependencies, persons with nicotine dependence had higher rates of major depression and anxiety disorders. The strength of these associations varied by level of severity of nicotine dependence. Nondependent smokers had higher rates of other substance dependencies, but not of major depression or anxiety disorders.