Classic formulations by Freud claim that the turning of hostility away from the object world and onto the ego is a crucial mechanism in the psychogenesis of depression. In light of Freud's “retroflexed anger” theory of depression, it follows that tricyclics would increase outward-directed hostility (hostility-out) and decrease inward-directed hostility (hostilityin). Previous research has not confirmed the expected relationship between verbalized affect and imipramine, but these studies did not verify that patients received a clinically effective dose. Using the Gotteschalk verbal sample technique, the present study measured hostility directed inward and outward of eight nondelusional endogenous depressives who received imipramine in placebo, subclinical, and clinical doses. Hostility-out was found to increase significantly only when patients obtained plasma levels of imipramine considered to be clinically effective (11). Hostility-in was unrelated to imipramine, but a nonsignificant trend of lowered anxiety was found for both subclinical and clinical plasma levels of imipramine. All of the changes in verbalized affect were observed within a postdrug period which predated overt clinical change. Hence, the relationship of subclinical and clinical plasma levels of imipramine to verbalized affect was considered to serve as a behavioral index of clinically effective plasma levels of imipramine which could be predictive of favorable outcome.