• Conjunctival and nasopharyngeal cultures for Chlamydia trachomatis were obtained from infants 30 days of age or younger with purulent conjunctivitis. Conjunctival specimens were also tested for other bacterial pathogens and for viruses. Most of the infants studied were black and came from a low-income, urban population. By random assignment infants received either topical treatment with 10% sulfacetamide sodium ophthalmic solution or systemic treatment with oral erythromycin estolate (50 mg/kg/day). Treatment was continued for 14 days if C trachomatis was isolated from the conjunctivae. Treatment was considered to be effective if conjunctivitis resolved and if follow-up chlamydial cultures of the conjunctivae and nasopharynx were negative at completion of therapy and two to four weeks later. Chlamydia trachomatis was isolated in the absence of other pathogens from the eyes of 37 (73%) of 51 infants with conjunctivitis. Other bacterial pathogens were isolated from four infants (8%) and viruses from none. Chlamydial infection was eradicated from 14 (93%) of 15 infants treated orally. In contrast, persistent conjunctival infection was detected in eight infants (57%) and nasopharyngeal colonization in three (21%) of 14 infants after topical treatment. It was concluded that C trachomatis is the most frequent cause of neonatal conjunctivitis in the low-income, urban population studied; that erythromycin estolate administered orally for 14 days eradicates chlamydial conjunctival and nasopharyngeal infection; and that topical sulfacetamide therapy may result in persistent conjunctival infection and nasopharyngeal colonization.