Classic genetic studies utilizing twin methods, adoption and cross-fostering data and pedigree analysis, have confirmed the hypothesis that the familial component in affective disease is biological, rather than social or environmental. Only recently, however, has it been possible to clarify the mode of inheritance of affective disorder or to identify specific DNA segments which are physically linked to genes conferring susceptibility to affective illness. At present, two susceptibility genes have been identified in individual families, and it is certain that additional vulnerability genes remain to be identified. Thus, affective illness is said to be genetically heterogeneous; i.e., different genes confer susceptibility in different families. Empiric risk figures suggest that the first degree relatives of a person with affective illness have about a 25-30% liability of major depression or manic-depressive illness, as compared to a population risk of 3-6%. Second degree relatives have a 12-15% risk, and third degree relatives a 6-9% risk. Pedigree studies strongly suggest that these figures represent the arithmetic mean of a high risk in families "loaded" for affective disorder, and a low risk in families with sporadic occurrence of the same illness. These data would argue that it is incumbent upon any physician to determine whether individual patients have a familial or non-familial form of affective illness, and to inform the patient accordingly.