A 26-year-old man experienced a Gell-Coombs type I allergic reaction to tetracycline hydrochloride, which had been given as therapy for nongonococcal urethritis. The patient had a history of allergy to penicillin and of asthma. The allergic response to tetracycline resolved after administration of epinephrine and diphenhydramine. Since tetracycline is often used for treatment of sexually transmitted diseases, physicians should be aware of the possibility of an allergic response to this drug.