Although definitive studies regarding the correlation between tricyclic antidepressant plasma levels and therapeutic effect are lacking, preliminary data suggest that measurement of tricyclic antidepressant plasma levels provides a rational approach to improve clinical management of the depressed patient. Data were collected to determine if the routine measurement of plasma tricyclic antidepressant levels was practical in a large clinic population, and to determine if such levels could improve patient care. Individual differences in drug metabolism and frequent unreliable ingestion of medication make the measurement of drug plasma levels the only sure means of determining if a patient is receiving a fair therapeutic trial on a particular tricylic antidepressant. Plasma analysis revealed both the failure to ingest adequate amounts of medication as prescribed and also the abuse of medications. Although generalizations regarding individual variation in drug metabolism or generalizations concerning drug compliance do little to improve patient care, whenever such problems are met on an individual basis, many clinical management problems can be resolved.