Antibiotics for the treatment of group B streptococcal (GBS) infection are usually given for 7-10 d. The aim of this prospective investigation was to study whether antibiotic treatment for 6 d is sufficient to treat early-onset GBS infection in term and near-term neonates. During a 2 y period 67 neonates of GBS-positive mothers developed GBS infection and were admitted to the neonatal intensive care unit. All neonates showed clinical signs of infection, C-reactive protein levels > 20 mg/l and/or elevated immature to total neutrophil ratio > 0.25. Two groups were differentiated: 10 neonates with proven sepsis with GBS-positive blood cultures (15%) and 57 neonates with presumed GBS infection with negative blood cultures but with GBS-positive surface swab cultures of ear (68%), nasopharyngeal (21%) or gastric aspirate (16%). All patients were GBS positive in 1 or more cultures. Antimicrobial therapy with ampicillin and cefotaxime was discontinued after 6 d. At that time all neonates were asymptomatic and laboratory results were normal. No relapse or death within 4 weeks after therapy was detected. In conclusion, antibiotic therapy for 6 d was sufficient to treat 10 neonates with proven and 57 neonates with presumed early-onset GBS infection. Owing to the small sample size, further studies are needed to show significant differences to longer therapy regimens.