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We have recently seen two cases of ophthalmia neonatorum (ON) that illustrate a changing picture of this disease and raise a number of questions concerning optimal prophylaxis and treatment. Silver nitrate, which is the most widely used method for prevention of gonococcal ON, fails to prevent neonatal eye disease due to chlamydia. In addition, strains of gonococci which produce a penicillinase and are resistant to penicillin are becoming common in parts of the United States and Europe. Thus all gonococcal isolates must be tested for penicillinase production. The emergence of Chlamydia trachomatis as the most frequent cause of ON and the appearance of penicillin-resistant gonococci has led to new regimens for prophylaxis and therapy of neonatal ophthalmia. At our institution, we now use intramuscular penicillin and topical tetracycline ointment (1%) for eye prophylaxis. For initial therapy of gonococcal ON we recommend penicillin (systemic and topical) plus another antimicrobial with greater stability against the penicillinase of Neisseria gonorrhoeae.