The purpose of this study was to examine the maternal risk factors associated with early onset Group B streptococcus (GBS) sepsis and determine the potential impact of intrapartum chemoprophylaxis using these risk factors. Using a computerized perinatal database, 26,525 deliveries over a five-year period (1989 to 1994) were identified. Neonates with GBS-positive cultures were identified and the neonatal and maternal chart of each case was reviewed. Twenty-six neonates (1 of 1000) had GBS sepsis documented by blood or cerebrospinal fluid culture. Maternal risk factor(s) were identified in 13 (50%) cases: preterm labor (5), preterm premature rupture of the membranes (5), prolonged rupture of membranes (6), sibling affected by symptomatic GBS infection (2), or maternal fever during labor (5). There were four mothers whose neonates had GBS sepsis in spite of intrapartum antibiotics. Intrapartum chemoprophylaxis for GBS based on risk factors alone will identify only half of the neonates who develop disease. Extension of intrapartum chemoprophylaxis to patients with risk factors appears to be necessary to prevent early onset disease in the other half. Since 85.7% of our total obstetrical population has no risk factors, this policy would require treating 1749 women to prevent one case of GBS sepsis. Chemoprophylaxis could be more appropriately targeted if mothers colonized with GBS could be identified in early labor.