This review, together with Part 1 (Clin. Chem. 26: 5-17, 1980), summarizes progress in measurement of tricyclic antidepressants in biological fluids and the application of the methodology to clinical practice. For many of the older drugs and for all of the new-generation antidepressants, further studies are required to delineate the precise relationship between plasma concentration and clinical response in well-defined diagnostic groups. For new drugs, rigorous evaluation of a method of measurement is required before it is applied to clinical studies. Assessment of drug interactions, inter-patient variability in plasma concentrations, and determination of the plasma concentrations required for therapeutic response all depend almost entirely on the quality of the assay methodology.