Random regression models (RRMs) were used to investigate the role of initial severity in the outcome of 4 treatments (cognitive-behavior therapy [CBT], interpersonal psychotherapy [IPT], imipramine plus clinical management [IMI-CM], and placebo plus clinical management [PLA-CM]) for outpatients with major depressive disorder seen in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Initial severity of depression and impairment of functioning significantly predicted differential treatment effects. A larger number of differences than previously reported were found among the active treatments for the more severely ill patients; this was due, in large part, to the greater power of the present statistical analyses.