Objective: To determine the aetiologies and clinical characteristics of infants with fever and a bulging fontanelle. Design: The medical records of all febrile infants with a bulging fontanelle who underwent a lumbar puncture from January 2000 to February 2008 in Assaf Harofeh Medical Center, a university affiliated hospital in central Israel, were identified. Results: 153 patients met the inclusion criteria. The male to female ratio was 100:53; age range was 3-11 months with a mean age of 5.6 (SD 1.8) months and a median age of 5 months. Cerebrospinal fluid pleocytosis was found in 42 cases (27.3%), including one case of bacterial meningitis (0.6%). Other leading diagnoses were aseptic meningitis (26.7%), upper respiratory tract infection (18.3%), viral disease not otherwise specified (15.6%), roseola infantum (8.5%) and acute otitis media (6.5%). Appearance on admission was described as good to excellent in 113 (73.8%) infants, none of whom had bacterial meningitis. 32 had aseptic meningitis and 17 had other bacterial disease (pneumonia, acute otitis media, pyelonephritis, bacteraemia, shigella or salmonella gastroenteritis). All the latter had, upon admission, symptoms, signs, laboratory tests or imaging studies suggesting a bacterial aetiology. Conclusions: In this large cohort, all infants who appeared well on admission and had normal clinical, laboratory and imaging studies had benign (non-bacterial) disease. In an infant who appears well and has no evidence of bacterial disease, it is reasonable to observe the infant and withhold lumbar puncture. Prospective studies should be carried out to confirm this approach.