The major psychoses have been investigated for genetic and environmental etiological factors for over two centuries. Recent emphasis has been placed on a genetic (diathesis) environmental stress model. For schizophrenia, manic-depressive, and schizo-affective psychoses, research evidence from psycho-biological studies, family, pedigree, twin, and adoptee studies has provided sufficient data from diagnostic and follow-up studies and new psychopharmacological research that for these three major psychoses a strong necessary but not sufficient basis for genetic causation exists. This review attempts to summarize existing data into a hypothesis that suggests that two separate gene pools of polygenic nature relate to the development of schizophrenia and manic-depressive illness and that schizo-affective illness may result from genetic transmission from each of these separate gene pools. The hypothetical model for each psychosis proposes that polygenetic inheritance affects different central nervous system neuroanatomical sites in the human which are in homeostasis as to catecholamine neurotransmitter regulation of the psyche. With sufficient environmental stress, an "imbalance" occurs in the neural integrative systems which produces phenotypically the three separate psychotic behavioral syndromes of schizophrenia, manic-depressive psychosis, and schizo-affective psychosis.