A multicentre comparative clinical evaluation of lofepramine, an imipramine analogue, and imipramine has been made with double blind technique and fixed dosage (lofepramine 70 mg t.i.d., imipramine 50 mg t.i.d.). Plasma was drawn after 3 weeks for determination of noradrenalhe‐uptake inhibitory capacity of the parent compound and or its active metabolites. Plasma concentrations of lofepramine and desmethylimipramine (DMJ) were determined in the same samples. The concentrations of lofepramine in the whole material were low (5–27 nglml) except for one patient who had a level of 53 ng/ml. In both groups of patients there was an almost 40‐fold range in the plasma levels of DMI or a parent DMI. The patients were rated for severity of depression before treatment, then once weekly for 3 weeks and finally during the Hth weak. For further information concerning the psychiatric aspects, seedElia et al. in this issue (1977). A significant correlation was found between the concentrations of DMI and the noradrenalinauptake inhibitory capacity in the plasma sample. No correlations were found between uptake inhibitory capacity of plasma samples and the amelioration s