Context: A major criterion to validate diagnoses is stability over time. Objective: To examine the stability of several classification systems for lifetime diagnosis of alcohol dependence, to identify characteristics predicting stability of alcoholism, and to study stability of lifetime assessments of habitual smoking (1 pack per day for at least 6 months) and other drug dependence. Design: Participants in the Collaborative Study on the Genetics of Alcoholism were interviewed using the Semi-Structured Assessment for the Genetics of Alcoholism and reevaluated 5 years later. Initial and follow-up interviews were available for 1728 individuals (641 index cases, 800 siblings, 287 controls) with lifetime diagnoses of alcohol dependence, other substance dependence (marijuana, cocaine, other stimulants, sedatives, opioids), or habitual smoking at first interview. The likelihood that an individual with a lifetime history of substance dependence or habitual smoking at the first interview retained this classification after 5 years was examined to assess stability of diagnosis. Results: Stability of a lifetime diagnosis of alcohol dependence varied among the subject groups of index cases, siblings, and community-based controls. Alcohol dependence as defined by DSM-III-R criteria was highly stable in the index cases (90.5% women, 94.7% men) but much less stable in the community-based controls (27.5% women, 64.7% men). The most important characteristic associated with stability of diagnosis of alcohol dependence was severity, defined by the number of alcoholrelated symptoms. Other DSM-III-R substance dependence disorders varied in the stability of diagnosis over a 5-year period. Lifetime history of habitual smoking was highly stable in all subject groups (96.0% overall). Conclusions: Stability of lifetime assessment of alcohol dependence varies depending on severity of illness. Severe cases of alcohol dependence are more likely to be stable, whereas general population cases of alcohol dependence are less likely to have stable diagnoses. The stability of diagnosis for other substance dependence varies from substance to substance.