ABSTRACT Mean effect sizes for changes in depression were calculated for 2,318 patients who had been randomly assigned to either antidepressant medication or placebo in 19 double-blind clinical trials. As a proportion of the drug response, the placebo response was constant across different types of medication (75%), and the correlation between placebo effect and drug effect was .90. These data indicate that virtually all of the variation in drug effect size was due to the placebo characteristics of the studies. The effect size for active medications that are not regarded to be antidepressants was as large as that for those classified as antidepressants, and in both cases, the inactive placebos produced improvement that was 75% of the effect of the active drug. These data raise the possibility that the apparent drug effect (25% of the drug response) is actually an active placebo effect. Examination of pre-post effect sizes among depressed individuals assigned to no-treatment or wait-list control groups suggest that approximately one quarter of the drug response is due to the administration of an active medication, one half is a placebo effect, and the remaining quarter is due to other nonspecific factors.