Inappropriate plasma drug concentrations may be one major reason why many patients fail to show a satisfactory clinical response or experience side-effects to treatment with tricyclic antidepressants. One way of improving the situation is to try to reduce the variability in plasma concentrations by individualising drug dosage regimens as early as possible in treatment. This could be done if it were possible to predict the steady-state plasma concentrations that would be achieved by patients on any given dosage regimen. Our own studies, as well as those of other groups, have demonstrated that it is possible to make such predictions from simple measurements of drug plasma concentrations after administration of a single test dose of antidepressant. The test is best carried out in addition to therapeutic monitoring and is a simple means of selecting the optimum starting dose. The clinical advantages of a simple tolerance test are (1) ensuring that an appropriate dosage is prescribed, (2) reducing the number of dosage alterations, (3) reducing the risk of toxicity, and (4) checking patient compliance when used in combination with routine therapeutic monitoring.