All published studies on the familial incidence of schizophrenia appropriate for testing the applicability of the general single-locus two-allele model are examined under the assumption of a unitary etiology for all schizophrenia. We show that the single major locus model is inadequate to predict the incidence in four classes of relatives of schizophrenic probands (parents, siblings, monozygotic, and dizygotic cotwins). In addition, the observed proportion of affected offspring from dual matings differ significantly from the model's prediction. The lack of an overall fit between the published familial distributions and the monogenic model suggests that a single major locus is insufficient for the etiology of schizophrenia. Further efforts in examining multifactorial models, mixed models, and other transmission models may be fruitful.