Fifty depressed in-patients at two psychiatric units, one in Italy the other in England, were treated with clomipramine, either orally, or intravenously and orally. A comparison of clinical response with plasma levels of clomipramine and its metabolite, desmethylclomipramine, showed clear relationships especially in the case of desmethylclomipramine. In the intravenously-treated group this was linear, in the orally-treated group it was curvilinear. Plasma levels of desmethylclomipramine and administered clomipramine correlate highly. These findings, together with the fact that significant clinical improvement was observed in only 55% of the patients, suggest that titration of the administered dose to obtain more effective plasma levels of the metabolite might improve the clinical response to the drug in some patients.