Timolol is widely used in glaucoma treatment without sufficient knowledge of its vascular retinal effects. In this study, we measured the retinal vessel diameters before and after instillation of 0.5% timolol twice daily in one eye for 1 week, using photographic enlargements (x44). A total of 12 normal, caucasian subjects aged 25-39 years (average, 30.6 +/- 4.2 years) participated in this study. In all, 75% of the subjects had a diminution of retinal arterial size in the treated eye. The mean arterial diametric decrease was 4.1% in treated eyes compared with both untreated eyes and pretreatment values of treated eyes. These diminutions were statistically significant according to Student's paired t-test (P less than 0.05). No statistical difference was found in venous diameters (t = -0.065). Results showed that 0.5% timolol may have a vasoconstrictive effect on the retinal arteries of normal human subjects after 1 week of unilateral instillation twice daily. We suggest that this arterial vasoconstriction could be caused by the effect of timolol on the vascular beta-2 receptors. Further investigations are warranted to determine whether timolol also acts on ciliary arteries and whether arterial vasoconstriction participates in lowering intraocular pressure.