Multiple factors have been described as significant contributors to depression in medical patients. This study attempts to assess the relative significance and interrelationship of variables associated with depression. A group of 199 family practice patients were studied. Using a multivariate research design, significant depressive symptoms were found in 41% of the sample. A stepwise multiple regression analysis revealed that the five most important factors associated with depression, in order of significance, were socioeconomic status, recent stress, use of birth control pills, serious physical illness, and distant life events. This study supports the thesis that depression is a final common pathway syndrome in which biologic and social forces coalesce into syndrome expression. The primary care practitioner needs to be aware of the multiple risk factors for depression to develop effective detection and intervention strategies.