Risk indicators play an important role in the active prevention of neonatal Early-Onset GBS-related Disease (EOD). We studied the associations between potential risk indicators and the occurrence of EOD by means of a case-control study. All cases of EOD delivered in the Academic Medical Centre in Amsterdam between January 1988 and December 1995 were included. For each case we selected 3 controls, matched for date and time of birth. The association between continuous risk indicators and the occurrence of EOD was assessed using spline functions. Multivariable logistic regression analysis was performed to determine which risk indicators contributed independently. Forty-one cases were compared with 123 controls. In the multivariable analysis, gestational age < 37 weeks and intrapartum temperature > or = 37.4 degrees C showed to be statistically significant risk indicators for EOD, with odds ratios of 2.5 per week gestation and 1.6 per 0.1 degree C, respectively. After cesarean section the risk of EOD was significantly decreased (OR 0.13). Of the other potential risk indicators only prelabor rupture of membranes showed an increased risk, although the association was not statistically significant. Prolonged duration of ruptured membranes had no additional merit. Risk indicators that should be taken into account in strategies to prevent EOD are increased maternal temperature and decreased gestational age.