OBJECTIVES: We investigated the association between unemployment and early cause-specific mortality to determine whether the relationship was modified by other risk indicators. METHODS: Female and male twins (n=20632) were followed with regard to mortality from 1973 through 1996. Questionnaire data from 1973 were used to obtain information on experience of unemployment and on social, behavioral, health, and personality characteristics. RESULTS: Unemployment was associated with an increased risk of suicide and death from undetermined causes. Low education, personality characteristics, use of sleeping pills or tranquilizers, and serious or long-lasting illness tended to strengthen the association between unemployment and early mortality. CONCLUSIONS: An increased risk of death from external causes implies a need for support for those experiencing unemployment, particularly susceptible individuals.