In January, 2001 the forty-year followup phase of the U.S.-Danish Longitudinal Study of Alcoholism was initiated with funds provided by the government of Denmark. No funds were available to support the U.S. component of this longitudinal, high-risk alcoholism study that was first organized by the late Donald W. Goodwin, MD in 1976 and supported on two previous occasions by NIAAA (1979, 1989). We are requesting funds to support the continued U. S. involvement in this unique, prospective, high-risk study of male alcoholism. The 20-year followup phase compared high-risk sons of alcoholic fathers to low-risk sons of nonalcoholic fathers on hundreds of variables, extending back to their birth (before any became alcohol dependent) identifying dozens of putative risk factors. The 30-year followup found that 29 of 73 risk factors predicted alcohol drinking at that point in time. This final, 40-- year followup study assumes that most of the subjects will have passed the age of risk for developing alcoholism and that some who did drink alcoholically in the past, no longer do so. The 40-year followup will test the predictive power of previously found risk factors and will identify other influences, over the subjects lifetime, that independently and collectively initiated, sustained or protected the individual from alcoholic drinking. From the onset, this joint U.S.-Denmark study of alcoholism separated the research into two components. The Danish component was responsible for identifying, locating and examining the 357 subjects initially selected for study from a large birth cohort developed in Copenhagen. The U.S. component accepted responsibility for protocol development, instrumentation, data entry and primary data analyses. The U. S. component created the existing data system that codes information obtained from all phases of the study, including the neonatal phase, the 20-year phase, the 30-year phase and now the 40- year followup phase. A total of 8,262 separate pieces of information on each subject have now been integrated into a single SAS database. A 100-page Dictionary of Variables is available that contains the name, location, range, and code definitions of each variable. More information will be added during the 40-year follow-up that will include a thorough review of drinking and its effects as well as a systematic survey of the major DSM-IV syndromes. The fact that most of the information was collected prospectively, and from independent sources at different stages of the subjects' lives, provides the rare opportunity to search for, antecedents, and causes of male alcoholism in an enormously rich and varied database. Marc Schuckit, MD, a researcher experienced in conducting high-risk, longitudinal studies of alcoholism, will serve as our major consultant.