The role of interpersonal sensitivity in the relation between romantic stress and depression was examined in 55 adolescent girls from an inner-city high school. Depression, interpersonal sensitivity, and chronic and episodic romantic stress were measured at two time points, 6 months apart. Interpersonal sensitivity was found to moderate the longitudinal relation between romantic stress (both chronic and episodic) and depression. In contrast, interpersonal sensitivity did not potentiate depressive responses to non-romantic interpersonal stress, suggesting particular importance of stress in the romantic domain for adolescent girls. Results indicate that girls' sensitivities to romantic relationship stress should be specifically addressed in depression prevention and intervention programs.