A five-week clinical trial of the concurrent administration of topical timolol maleate and oral acetazolamide was conducted to determine the additivity of the ocular hypotensive effects of the two drugs. One drop of 0.5% timolol maleate, every 12 hours, produced a mean reduction in outflow pressure from baseline of 36.0%. When added to an eye pretreated with oral acetazolamide, timolol caused an additional mean decrease in outflow pressure of 27.6%. Acetazolamide, 500 mg orally every 12 hours, produced a mean reduction in outflow pressure from baseline of 48.6%. When added to an eye receiving topical timolol, oral acetazolamide caused an additional mean decrease in outflow pressure of 43.2%. Concurrent administration of oral acetazolamide and topical timolol reduced outflow pressure only slightly less than the predicted reduction assuming full additivity of the drugs. This study supported the clinical usefulness of concurrent administration of acetazolamide and timolol to lower intraocular pressure.