AbstractSeventeen healthy volunters in three groups received no treatment, or 25 or 50 mg doses of amitriptyline. Maximal measured concentrations of amitriptyline occurred at 4 h post‐dosage. There was a dose‐dependent change in performance of a digit symbol substitution test. Visual analogue scales measuring drowsiness, speed of thinking, and lethargy were sensitive to the drug. The low dose induced no blood pressure changes, but tachycardia occurred. The higher dose induced hypotension with bradycardia, a hitherto undocumented reaction to the d