Dipivalyl epinephrine (dipivefrin) is a prodrug of epinephrine used for topical glaucoma therapy. Local side effects have been noted in approximately 20% of patients treated and include conjunctival hyperemia, foreign body sensation, and follicular conjunctivitis. We studied five patients with adverse local reactions to dipivefrin (Propine) eye drops. Propine contains the following: dipivefrin, 0.1%; mannitol, 1.89%; sodium metabisulfite, 0.075%; disodium edetate, 0.0127%; and benzalkonium chloride, 0.004%. Since the reactions could conceivably have been caused by an ingredient other than dipivefrin, we first patch tested the patients with the maximum recommended concentration of each ingredient. All patch tests were negative. Sterile ophthalmic solutions of each individual component at the concentrations used in the commercial product were then prepared. In a double-blinded study, the patients applied two drops of each preparation, twice daily for 1 week, with a 1-week, drug-free period between trials. Dipivefrin alone reproduced each patient's initial Propine-induced conjunctivitis; symptoms occurred unilaterally in one patient and bilaterally in the other four patients. This study indicates that testing with single component eye drops can identify the provocative component in ocular drug hypersensitivity and that these reactions can be unilateral.