Platelet monoamine oxidase (MAO) activity, psychiatric disorders, and family history of psychopathology were studied in 115 nonhospitalized, previously undiagnosed college student volunteers. Subjects were classified into two extreme groups: those with platelet MAO activity two standard deviations below the mean ("low-MAO" probands) and those with platelet MAO activity two standard deviations above the mean ("high"-MAO probands). Low-MAO probands were found to have a significant increase in the incidence of borderline schizophrenia and other psychiatric disorders compared to high-MAO probands. First-degree relatives of low-MAO probands were more often affected with psychiatric disorders and borderline schizophrenia than relatives of high-MAO probands. The data suggest that reduced platelet MAO activity is associated with psychiatric vulnerability and that the spectrum of schizophrenia may be more closely related to this vulnerability than other psychiatric disorders.