In communities with endemic blinding trachoma, mass (or "blanket") treatment with a topically applied tetracycline derivative is a standard control measure. The widely used "intermittent" treatment schedule consists of the twice daily application of antibiotic ointment for five consecutive days once a month for six months. In this study, the efficacy of "intermittent" treatment was evaluated for the treatment of severe and moderate intensity trachoma in children in southern Tunisia. Tetracycline or erythromycin ointments (specific antichlamydial drugs) were compared with 5% boric acid ointment (a simple antiseptic) given by the intermittent schedule during the winter and spring. There was a statistically significant degree of improvement at only one examination, four weeks after the full course of treatment had been completed. When re-examined five months later there were no differences in intensity in the three groups. The limited effect of topical chemotherapy might be attributable to several causes, among which could be inadequate drug levels, inadequate treatment periods, reinfection from non-treated children in the community, and auto-infection from extraocular sites (e.g., respiratory tract) in the same child. The possible value of short-term (two weeks) systemic antimicrobial therapy as an additional strategy to prevent blindness of children with potentially blinding active trachoma is discussed.