Negative cognitive structure (particularly for interpersonal content) has been shown in some research to persist past a current episode of depression and potentially to be a stable marker of vulnerability for depression (D. J. A. Dozois, 2007; D. J. A. Dozois & K. S. Dobson, 2001a). Given that cognitive therapy (CT) is highly effective for treating the acute phase of a depressive episode and that this treatment also reduces the risk of relapse and recurrence, it is possible that CT may alter these stable cognitive structures. In the current study, patients were randomly assigned to CT+ pharmacotherapy (n = 21) or to pharmacotherapy alone (n = 21). Both groups evidenced significant and similar reductions in level of depression (as measured with the Beck Depression Inventory-II and the Hamilton Rating Scale for Depression), as well as automatic thoughts and dysfunctional attitudes. However, group differences were found on cognitive organization in favor of individuals who received the combination of CT+ pharmacotherapy. The implications of these results for understanding mechanisms of change in therapy and the prophylactic nature of CT are discussed. (Contains 3 figures and 4 tables.)