Administration of timolol to one eye is associated with a decrease in intraocular pressure in both eyes. To further investigate this effect the contralateral decrease in intraocular pressure was measured in a three arm crossover study using a 0.1 mg dose of timolol given topically to an eye, a 0.1 mg dose of timolol given lingually, and a placebo given topically. Two hours after topical timolol administration the mean intraocular pressure reduction in the fellow eye was 3.1 mm Hg compared with baseline (p = 0.0007). Two hours after lingual timolol administration the mean intraocular pressure reduction was 3.9 mm Hg compared with baseline (p = 0.0004). Two hours after topical administration of placebo the mean intraocular pressure reduction in the fellow eye was only 0.33 mm Hg (p = 0.6). These findings suggest the contralateral reduction in intraocular pressure from timolol is caused by systemic absorption. The significant intraocular pressure reduction obtained from lingual timolol raises the possibility that this route of drug administration may be useful in selected patients who cannot use eye drops.