The efficacy of treatments for depression is often measured by comparing observed total scores on self-report inventories, in both clinical practice and research. However, the occurrence of response shifts (changes in subjects' values, or their standards for measurement) may limit the validity of such comparisons. As most psychological treatments for depression are aimed at changing patients' values and frame of reference, response shifts are likely to occur over the course of such treatments. In this article, we tested whether response shifts occurred over the course of treatment in an influential randomized clinical trial. Using confirmatory factor analysis, measurement models underlying item scores on the Beck Depression Inventory (Beck & Beamesderfer, 1974) of the National Institute of Mental Health Treatment of Depression Collaborative Research Program (Elkin, Parloff, Hadley, & Autry, 1985) were analyzed. Compared with before treatment, after-treatment item scores appeared to overestimate depressive symptomatology, measurement errors were smaller, and correlations between constructs were stronger. These findings indicate a response shift, in the sense that participants seem to get better at assessing their level of depressive symptomatology. Comparing measurement models of patients receiving psychotherapy and medication suggested that the aforementioned effects were more apparent in the psychotherapy groups. Consequently, comparisons of observed total scores on self-report inventories may yield confounded measures of treatment efficacy.