A retrospective analysis was performed of 109 previously well infants younger than 4 weeks of age with a history of fever who were evaluated for sepsis in an emergency department. The objective was to assess whether infants who were afebrile at the time of evaluation were at similar risk for serious bacterial infection compared with infants with documented fever at the time of evaluation. Of 109 infants evaluated 54 were afebrile and 55 had fever (rectal temperature, greater than 38 degrees C). Serious bacterial infection occurred in 8 (14.5%) infants with documented fever and in none of those who were afebrile at the time of presentation (P = 0.003). An initial complete blood count profile of the two groups showed that nearly all (96%) in the afebrile group had a complete blood count differential ratio [% of lymphocytes + % of monocytes)/(% of polymorphonuclear leukocytes + % band forms] of greater than 1, whereas the majority (87.5%) of febrile infants with serious infection had a differential ratio of less than 1. The neonate with a history of fever who is afebrile upon presentation should receive a complete evaluation for possible bacterial infection. The neonate who appears well, has no focal source of infection on examination and whose laboratory data do not reveal any abnormality represents a low risk for serious bacterial infection.