Peripheral anticholinergic activity of single acute doses of three tricyclic antidepressants (amitriptyline 50 mg, desipramine 50 mg, doxepin 100 mg) and placebo was assessed by several physiologic measures in normal male volunteers. Amitriptyline and doxepin produced similar significant depressions in salivary flow and finger sweating compared to placebo, while desipramine produced no change. Supine and standing blood pressures and standing pulse yielded significant differences among the drugs. Measures in at least three areas (salivation, perspiration, and pulse-blood pressure) offer a simple and reliable battery of tests for the peripheral autonomic effects of tricyclic antidepressants.