Concomitant plasma and serum tricyclic determinations were performed on 20 patients chronically administered imipramine (N = 10), amitriptyline (N = 10), desipramine (N = 10), and nortriptyline (N = 10). Plasma levels for these tricyclic antidepressants were significantly greater than the corresponding serum levels. Plasma-serum differences for the secondary amines (DMI/NT) were more than twice those for the tertiary amines (IMI/AMI). The authors thus suggest that clinicians and investigators specify the specific source of blood sample when assessing blood levels of the secondary tricyclic antidepressants.