Emperical support for genetic heterogeneity in alcoholism from the Stockholm Adoption Study and related studies is described. Evidence for distinct alcoholic subtypes in Swedish adoptees has been replicated and extended in other samples in Sweden and the United States by means of clinical interviews, prospective longitudinal studies, pedigree and neurophysiological studies. A general theory of neurogenetic adaptive mechanisms has been described and supported by clinical, genetic and neuropharmacological results. Littrell's comments on the Swedish adoption studies contain fundamental errors of fact, logic and concept that infirm her conclusions. Alternative hypotheses suggested by Littrell to explain paternal and maternal inheritance patterns without distinguishing subtype-specific genetic factors cannot account for the observed data. Alcoholic subtypes can now reliably be distinguished using operational diagnostic criteria based on explicit alcohol-related symptoms or personality traits allow predictions of individual differences at risk for adult alcoholism and associated neurobiological characteristics. The underlying personality traits also explain the comorbidity of alcoholism with other psychopathology. These theoretical and methodological advances should facilitate further efforts to generalize and extend prior research.