Group B streptococci remain a serious cause of morbidity and mortality in neonates. GBS vaccine or immunoglobulin administered iv may enhance neonatal GBS immunity. Likewise, intrapartum antibiotic therapy of colonized mothers appears to reduce vertical transmission of group B streptococci and to prevent both maternal and neonatal GBS disease. However, the safety and effectiveness of routine penicillin prophylaxis less than or equal to 1 hr after birth remain in question. For example, penicillin prophylaxis appears to be of little value in infants with low birth weights (less than 2,000 g) who become symptomatic shortly after birth; however, it may reduce the incidence of disease in larger, full-term infants who acquire the group B streptococci at delivery or in the few hours immediately thereafter. The potential harm of administering penicillin to all neonates must also be considered, since routine antibiotic therapy may alter the incidence of both neonatal infections due to penicillin-resistant pathogens and possible later penicillin allergy. Theoretically, a single injection of penicillin at birth may suppress GBS disease in some neonates but not effectively treat it, allowing the disease to progress prior to diagnosis and therapy. The decision to use penicillin routinely in neonates to prevent GBS disease must therefore be made with caution. Presently, this decision must be made on a situational basis, with institutions having a high incidence of early-onset GBS disease electing to use penicillin only if the potential benefits outweigh the risks.