Objective: In the present study, we examined the relationship between posttraumatic and depressive symptoms during prolonged exposure (PE) treatment with and without cognitive restructuring (CR) for the treatment of posttraumatic stress disorder (PTSD). Method: Female assault survivors (N = 153) with PTSD were randomized to either PE alone or PE with added CR (PE/CR). During treatment, bi-weekly self-report measures of posttraumatic and depressive symptoms were administered. Results: Multilevel mediational analyses indicated that during PE, changes in posttraumatic symptoms accounted for 80.3% of changes in depressive symptoms, whereas changes in depressive symptoms accounted for 45.0% of changes in posttraumatic symptoms. During PE/CR, changes in posttraumatic symptoms accounted for 59.6% of changes in depressive symptoms, and changes in depressive symptoms accounted for 50.7% of changes in posttraumatic symptoms. Conclusions: This pattern of results suggests that PE primarily affects posttraumatic symptoms, which in turn affect depressive symptoms. In contrast, PE/CR results in a more reciprocal relationship between posttraumatic and depressive symptoms. (Contains 2 tables, 2 figures, and 4 footnotes.)