From July 1991 through June 1994 we implemented a program of screening for GBS colonization (reported in part Gibbs, Obstet Gynecol 1994;84:496-500). 952/5063 (18.8%) of mothers screened were GBS positive. Mothers positive for GBS with high-risk factors (chorioamnionitis, preterm birth, ROM >12 hours at term) were given intrapartum ampicillin. During this prospective study there were two cases of GBS sepsis despite maternal chemoprophylaxis. One at term in a mother with chorioamnionitis treated for 2.5 hours and the other at 29 weeks gestation despite 116 hours of ampicillin. We previously reported (Weisman, J Pediatr 1992;121:428-33) fever/chorioamnionitis in 24/25 cases of GBS sepsis with chemoprophylactic failure. As previously reported, maternal chemoprophylaxis failures occur in high-risk term infants who receive less than 4-8 hours of intrapartum therapy or in preterm infants. Conclusion: Although maternal chemoprophylaxis for maternal high-risk factors is not necessarily an indication for neonatal antibiotic treatment, infants of mothers who are GBS positive and have high-risk factors of prematurity or fever/chorioamnionitis should be treated for GBS sepsis despite maternal chemoprophylaxis.