Studies of the occurrence of mental illness in families have been useful in identifying familial forms of the illnesses but incompletely specify the nature and strength of genetic and environmental factors in etiology. We have previously reported that chronic schizophrenia-like disorders occur at a significantly elevated rare in the biological relatives of chronic schizophrenic adoptees and not in their adoptive relatives. Our recent replication of this finding in a national register of nearly 15,000 Danish adoptees provides compelling evidence for the significant operation of genetic factors in the etiology of schizophrenia. Furthermore, our demonstration that the familial tendency in this disorder is and expression of genetic transmission and to search for genetic linkages. We are currently using our material to derive empirically based criteria for the diagnosis of schizophrenia and related disorders in order to enhance the validity of these diagnoses and to determine the boundaries of the schizophrenia spectrum of disorders.