Abstract: Identification and control of factors that are associated with placebo and drug response in acute mania may influence the design and analysis of future trials in this condition. We analyzed pooled data from 2 multicenter, placebo-controlled, randomized trials of divalproex sodium for the treatment of acute manic episodes, using linear and logistic regression to search for common and treatment-specific predictors of response. In both treatment groups, patients with greater numbers of prior hospitalizations, more severe baseline symptoms, or younger age at onset of illness were found to be significantly less likely to respond. The effect sizes associated with these factors were of comparable magnitude to the effect size associated with divalproex treatment. Stratification on the basis of these prognostic factors may improve the power of future trials for the treatment of acute mania and may help explain patient response to treatment.