Lowered activity of the enzyme MAOB in the platelets and other tissues of alcoholics than of nonalcoholics is the most replicated biological finding in genetic research in alcoholism. Data presented here and elsewhere also indicate that the relationship between MAOB activity and alcoholism extends to the clinical subtypes referred to as Type I and Type II alcoholism. A detailed examination of the relationship between in vitro platelet MAOB activity levels, alcoholic subtype, and general mental health status among the relatives of the probands suggests that low MAOB activity is a marker of increased risk overall and that the families of Type II alcoholics have a higher genetic risk loading than do the families of Type I alcoholics. This increased genetic loading is probably due to the classification of Type II alcoholics on the basis of features related to severity of illness and additional psychiatric features such as personality disorders. Although the families of alcoholics tend to have higher levels of psychiatric illness compared to the general population, the overall risk is compounded in the families of Type II alcoholics, and these differences in underlying risk are reflected in the observed differences in MAOB activities. Thus, MAOB is not a biological/genetic marker of alcoholism sensu stricto but is rather a biological/genetic marker of an underlying pathophysiologic process leading to alcoholism and other psychiatric illness. The task now before us is to understand this process and how the activity of MAOB is involved.