This study evaluated the relationship of sociotropic and autonomous personality traits with response to pharmacotherapy for 217 depressed outpatients using the Sociotropy-Autonomy Scale. Sociotropy was related to nonendogenous depression, whereas autonomy was related to endogenous depression. Subjects who had high autonomous-low sociotropic traits showed greater response to antidepressants (and greater drug-placebo differences) than those who had high sociotropic-low autonomous traits (who showed no drug-placebo differences). Hierarchical multiple regression analysis showed that the sociotropy-autonomy, but not the endogenous-nonendogenous, distinction was a predictor of drug treatment response. The combination of endogeneity and autonomy predicted response to placebo. If replicated, these findings may enable better matching of patient traits to various treatment modalities for depression.