The aim of the current study was to compare the pupil reaction to light in depressed patients and normal control subjects. Seven depressed patients with melancholic features according to DSM-IV criteria and 14 age- and gender-matched control subjects took part in the study. All were free of any medication for at least 2 weeks. All were aged between 25 and 50 years. An optical method was used to assess the pupil reaction to a single flash. Depressed patients manifested shorter latency for constriction than control subjects, and a marginal difference in the total work produced by acetylcholine. The results of the current study support the theory that there is a norepinephrine hypoactivity in melancholic depression, with less affected acetylcholine activity.