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Although prophylactic eyedrops to treat ophthalmia neonatorum is mandated nationwide, states and hospitals are free to choose specific drugs. To compare two of these agents, we studied the incidence and characteristics of ophthalmia neonatorum in two UCLA teaching hospitals over a five-year period. One, which used 1% silver nitrate solution exclusively, had 50 cases in 34,772 births, a frequency of 0.14%. The other used 0.5% erythromycin ointment exclusively and had 43 cases in 12,652 births, a frequency of 0.34%. Ophthalmia neonatorum was more frequent in the hospital using erythromycin (p less than 0.001), as was chlamydial conjunctivitis (p less than 0.02). Although not statistically significant, gonococcal conjunctivitis was found in four infants, all in the hospital using silver nitrate. Because silver nitrate was found more effective in decreasing the total frequency of all cases of ophthalmia neonatorum, and cases caused by Chlamydia and gram-negative bacteria specifically, this drug still should be considered as a primary prophylactic agent against ophthalmia neonatorum.