The case presented here involves a 32-year-old homosexual man with human immunodeficiency virus seropositivity and secondary syphilis. Because of possible penicillin allergy, he was initially treated with erythromycin base by mouth. During four weeks of therapy, his cutaneous lesions worsened as did his systemic symptoms. Following desensitization and parenteral penicillin therapy, his cutaneous lesions and symptoms rapidly resolved. His VDRL titer fell appropriately.