One of the side effects of antidepressant pharmacotherapy reported clinically is impairment of the sense of taste. In this study, the taste effects of four tricyclic antidepressant compounds (clomipramine HCl, desipramine HCl, doxepin HCl, and imipramine HCl) were evaluated experimentally by topical application of the drugs to the tongue. Taste detection threshold concentrations for all four medications ranged from 0.1 mM to 0.2 mM in young persons but were elevated by as much as 7.71 times that in elderly individuals who were taking no concurrent medications. Each compound had a predominantly bitter taste with other qualities including metallic, sour, and sharp-pungent. In addition, each tricyclic antidepressant at concentrations from 1 mM to 5 mM blocked responses to a wide range of taste stimuli in both humans and gerbils. The differential suppression of other tastes by tricyclic antidepressants at the level of the taste receptors may contribute to the clinical reports of dysgeusia and hypogeusia.