To assess prospectively the predictability of therapeutic dosage based on tricyclic antidepressant (TCA) concentrations after a single dose, 30 subjects were given amitriptyline. In the first 11 subjects maintained on a fixed amitriptyline dose regimen, predictive capacities of 18- and 24-hr single-dose levels were assessed and confirmed in relation to steady-state levels. For the other 19 subjects, the dose that would achieve a therapeutic steady-state concentration of 200 ng/ml was predicted from the 18-hr single-dose level and was rapidly instituted. Subjects achieved a mean steady-state TCA level of 204 ng/ml, with approximately 90% of the levels falling within the therapeutic range. There was clinical improvement within 2 wk in 84% of the subjects. Our results suggest that dose prediction based on TCA levels after a single dose is reliable and useful.