A total of 254 previously healthy outpatient neonates 31 days of age or younger with a rectal temperature ≥38°C were enrolled in a prospective study during an 18-month period to evaluate the validity of applying low risk criteria for bacterial infections in this population. All of the neonates received standard physical examinations and laboratory evaluations including blood and urine cultures at the time of admission. Those who had no evidence of ear, eye, soft tissue, umbilical or skeletal infection had between 5000 and 15 000 white blood cells/mm3, had a C-reactive protein of less than 20 mg/liter or an erythrocyte sedimentation rate less than 30 mm/ hour and a normal urinalysis were considered at low risk for bacterial infections. Bacterial infections were confirmed by cultures of the various body fluids. Bacterial infections were present in 17.7% (45 neonates) and bacteremia or meningitis in 5.1% (13 neonates). Eight (6.0%) of the 134 neonates who met the criteria had bacterial infections, while only 1 (0.7%) had bacteremia and meningitis, compared with 37 (30.8%) and 12 (10.0%), respectively, of the 120 who did not meet the criteria (bothP< 0.05). The negative predictive value of meeting the low risk criteria were 94.0% for excluding all bacterial infections and 99.3% for bacteremia and meningitis, respectively. Our data suggest that the criteria proposed here are useful in predicting febrile outpatient neonates at low risk for bacteremia or meningitis, but not for all bacterial infections. Our data support a recommendation for a complete work-up for sepsis, hospitalization and careful observation for febrile outpatient neo- nates who meet the suggested low risk criteria for bacterial infections, reserving the addition of parenteral antibiotic therapy for those who do not.