During a 2-year period, 233 infants younger than 3 months were prospectively studied to determine whether physical examination, white blood cell and band count, and urinalysis could identify infants unlikely to have serious bacterial infections. Only previously healthy infants (born at term, no perinatal complications, no previous or underlying diseases, no previous antibiotic therapy) were studied. One hundred forty-four (62%) of the 233 infants were considered unlikely to have serious bacterial infections, because they did not have physical findings consistent with ear, soft tissue, or skeletal infection, had between 5000 and 15,000 white blood cells/mm3, had less than 1500 bands/mm3, and urinalysis yielded normal findings. Eighty-nine (38%) infants did not meet one or more of these criteria and were classified as being at high risk for serious bacterial infection. Only one (0.7%) of the 144 infants in the low-risk group had a serious infection, compared with 22 (25%) of the 89 infants in the high risk group (P less than 0.0001). None of the infants in the low-risk group had bacteremia, compared with nine (10%) of the 89 infants in the high-risk group (P less than 0.0005). Neither traditional risk factors, such as age, sex, and temperature, nor other signs, symptoms, or laboratory findings were adequate predictors of serious bacterial infection. We conclude that previously healthy infants younger than 3 months with an acute illness are unlikely to have serious bacterial infection if they have no findings consistent with ear, soft tissue, or skeletal infections and have normal white blood cell and band form counts and normal urine findings.