Group B streptococcus is a leading cause of serious neonatal infection. Most neonatal GBS infections can be prevented through the use of intrapartum antimicrobial prophylaxis in women who are at increased risk for transmitting the infection to their newborns. However, despite clinical trials that demonstrate the effectiveness of intrapartum antibiotic prophylaxis, prevention strategies have not been implemented widely or consistently, and the incidence of neonatal GBS disease has not declined. To promote a coordinated approach to prevention among obstetric- and pediatric-care practitioners and among supporting clinical microbiology laboratory personnel, CDC has developed prevention guidelines in conjunction with experts from relevant disciplines and with representatives of the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and other professional organizations. This report provides the epidemiologic basis for prevention protocols, summarizes results of clinical trials demonstrating the efficacy of intrapartum antimicrobial agents, examines limitations of different approaches to prevention, and presents guidelines for the prevention of GBS disease. CDC recommends use of one of two prevention strategies. In the first strategy, intrapartum antibiotic prophylaxis is offered to women identified as GBS carriers through prenatal screening cultures collected at 35-37 weeks' gestation and to women who develop premature onset of labor or rupture of membranes at < 37 weeks' gestation. In the second strategy, intrapartum antibiotic prophylaxis is provided to women who develop one or more risk conditions at the time of labor or membrane rupture. Issues addressed by these prevention guidelines include the following: the appropriate clinical and laboratory methods required for prenatal screening programs designed to identify GBS carriers; risk conditions that indicate the need for intrapartum antibiotics; management of newborns whose mothers receive intrapartum antibiotic prophylaxis for GBS disease; and education of prenatal patients regarding GBS disease and the available prevention policy. These guidelines are intended for the following groups: a) providers of prenatal, obstetric, and pediatric care; b) supporting microbiology laboratories, hospital administrators, and managed-care organizations; c) childbirth educators; d) public health authorities; e) expectant parents; and f) advocacy groups for expectant parents.