We sought to evaluate the hypothesis that endogenous symptoms define a form of depression that is relatively distinct from a familial perspective. Cox models examined the relationship between endogenous symptoms in 88 epidemiologically ascertained cases of treated major depression and the risk for a range of psychiatric disorders in relatives. Endogenicity did not predict risk of major depression, bipolar disorder, anxiety disorders, schizophrenia, or schizophrenia spectrum illnesses in relatives. Risk in relatives of illness as an external validator of endogenous depression is not supported by our family study data.