A randomized clinical, trial to assess ocular hypotensive effect of sublingual administration of timolol was performed.Seventeen (9 male, 8 female; age range 45 to 68 years) with bilateral ocular hypertension were selected for the study. Each patient was evaluated with regard to IOP, arterial blood pressure and heart rate before and after each of the following experimental treatment: unilateral ocular administration of 20 microliters of 0.5% timolol solution; sublingual administration of 20 microliters of 0.5% timolol solution; unilateral ocular administration of 20 microliters of saline solution (placebo); sublingual administration of 20 microliters of saline solution (placebo). The sequence of the treatments and the eye topically treated were randomly chosen. At least four weeks wash-out elapsed between each experimental treatment.Our results showed that sublingual administration of timolol was able to induce a bilateral significant reduction of the IOP. This reduction was not statistically different from that obtained in the eye treated with timolol. A significantly greater reduction of the IOP was obtained by sublingual timolol than in the contralateral eye after unilateral topical administration of timolol solution. No significant modification of arterial blood pressure and heart rate were evidenced after the treatment.Sublingual administration seems to be a new interesting way for reducing the IOP. Long term studies are required in order to test efficacy and safety of this new treatment.