The purpose of this study was to assess whether nasolacrimal occlusion improves the therapeutic index of various antiglaucoma medications. Use of nasolacrimal occlusion resulted in better efficacy and safer usage. Nasolacrimal occlusion used with 2% pilocarpine, 1.5% carbachol, 0.25% timolol maleate, or 1% epinephrine every 12 hours gave the maximal response for these drugs. Applying 0.25% timolol and 1.5% carbachol every 12 hours gave the maximal response for this combination. Nasolacrimal occlusion did not alter the effect of 0.1% dipivefrin, and since the corneal penetration of this prodrug is 17 times that of epinephrine, 0.05% dipivefrin every 12 hours might be an adequate dosage for maximal effect. Our findings suggest that most of the commercially used antiglaucoma agents can achieve the same maximal effect with lower concentrations and less frequent administration (never exceeding every 12 hours). Nasolacrimal occlusion should markedly decrease systemic absorption and side effects following topical treatment.