We prospectively studied the value of the cocaine test in the diagnosis of Horner's syndrome, by performing the test in 20 control subjects and in 20 patients with a provisional diagnosis of Horner's syndrome. Photographic testing of the darkness reflex of the pupil was used as an independent criterion of oculosympathetic dysfunction, and confirmed the diagnosis in 12 of the 20 patients. A mydriatic response to cocaine that was at least 1.0 mm less than in the unaffected eye occurred only with Horner's syndrome (7 patients). On the other hand, if the difference is smaller than 1.0 mm the chance that the patient does not have Horner's syndrome is only around 60%. There was no relationship between the magnitude of the response to cocaine and the site of the lesion in the sympathetic system.