OBJECTIVE: To explore gender differences in depression vulnerability among an obese, treatment-seeking population and to discern those components of eating-related phenomena that discriminate the depression-comorbid obese from their noncomorbid counterparts. METHOD: This sample consisted of 1,184 self-admitted patients enrolled in a residential weight loss program between 1990 and 1995. Subjects were administered several questionnaires including (a) the Beck Depression Inventory, (b) 5-point scales of eating-related foci, and (c) 7-point scales of subject's confidence in their eating control under various circumstances. Data were analyzed via analyses of variance (ANOVAs) and stepwise regression. RESULTS: Greater depression was accompanied by more disruptive, dysregulatory eating tendencies, and stronger inclination to engage in affectively and socially disrupted eating. Regression results revealed gender-specific predictors of comorbid depression. For obese females, negative-emotion disrupted eating and binge-purge behaviors were prominent predictors of depression. For males, eating induced by experiences of social or physical inadequacy and fasting relating to eating behaviors were the depression-relevant variables. DISCUSSION: These results are discussed in terms of their theoretical implications for gender-mediated models of obesity-depression comorbidity, and in terms of their clinical significance.