Differences in action between imipramine (Tofranil®) and desipramine (Pertofran®), a metabolite of imipramine, in normal persons and in depressive patients are described. Correlations with the pharmacological findings of each comparative substance are discussed. If the comparison is limited to the therapeutic action, the two substances show rather similar properties, although there are some differences which seem to us important. On the other hand, the two comparative substances differ much more clearly in their effects in healthy subjects, where even opposite effects can be observed. Namely desipramine in the healthy subject shows a rather potent depressor effect and a slow onset of action, whereas in patients the drug has a short latent period and has a certain stimulant effect. Imipramine on the other hand acts rather slowly in patients but more quickly in healthy persons. It has scarcely any stimulant action, either in normal subjects or in depressive patients.