There has been increasing attention to the subgroups of mood disorders and their boundaries with other mental disorders, particularly psychoses. The goals of the present paper were (1) to assess the familial aggregation and co-aggregation patterns of the full spectrum of mood disorders (that is, bipolar, schizoaffective (SAF), major depression) based on contemporary diagnostic criteria; and (2) to evaluate the familial specificity of the major subgroups of mood disorders, including psychotic, manic and major depressive episodes (MDEs). The sample included 293 patients with a lifetime diagnosis of SAF disorder, bipolar disorder and major depressive disorder (MDD), 110 orthopedic controls, and 1734 adult first-degree relatives. The diagnostic assignment was based on all available information, including direct diagnostic interviews, family history reports and medical records. Our findings revealed specificity of the familial aggregation of psychosis (odds ratio (OR)=2.9, confidence interval (CI): 1.1-7.7), mania (OR=6.4, CI: 2.2-18.7) and MDEs (OR=2.0, CI: 1.5-2.7) but not hypomania (OR=1.3, CI: 0.5-3.6). There was no evidence for cross-transmission of mania and MDEs (OR=.7, CI:.5-1.1), psychosis and mania (OR=1.0, CI:.4-2.7) or psychosis and MDEs (OR=1.0, CI:.7-1.4). The strong familial specificity of psychotic, manic and MDEs in this largest controlled contemporary family study challenges the growing assertion that the major types of mood disorders are manifestations of a common underlying diathesis.