Portnoy B, Hanes B, Salvatore, MA, Eckert HL. J Pediatr 1966;68:181-8 Portnoy et al documented the peripheral white blood cell (WBC) counts in hundreds of hospitalized children with respiratory tract viruses, comparing children who were symptomatically and asymptomatically infected. The median WBC counts were significantly different: 14 465/mm3 in the symptomatic group vs 9000 in the asymptomatic group, but with large overlap. The hypotheses driving this investigation were not clearly stated by the investigators, but in the Discussion they speculated that the higher WBC counts in the symptomatic children may have been due in part to coincident infection by bacteria. The accurate identification of bacterial superinfection in viral respiratory tract illness remains a vexing problem. Influenza has a well-documented incidence of bacterial superinfection, most commonly with Streptococcus pneumoniae, particularly in fatal cases. Indeed, the name “Haemophilus influenzae” was derived from its original isolation from the lungs of persons suffering from severe influenza in the late 19th century. The frequency of bacterial superinfection in other viral respiratory tract infection is not well established. Respiratory viruses alter upper airway defenses, upregulate bacterial adhesion factors on epithelial cells, and disrupt elements of innate immunity in the lungs, so it is remarkable that even with influenza, the marked majority of lower respiratory tract infection in children is purely viral. The dilemma, then, has been to identify the few who are truly coinfected with bacteria, especially in severe disease, allowing the clinician to intelligently use or safely withhold antibiotics. Readily assessable variables such as fever, WBC count (as suggested by the data in Portnoy et al), and the acute phase reactant C-reactive protein insufficiently discriminate viral and bacterial disease in the individual child. Procalcitonin, a sensitive and specific acute phase reactant in detecting bacterial disease, was inadequate as a stand-alone test in identifying bacterial coinfection during the H1N1 influenza pandemic, although persistently low procalcitonin measurements may allow discontinuation of antibiotics once started. In the future, viral and bacterial or mixed viral/bacterial pneumonias may prove to have unequivocally distinct and measurable cytokine signatures, but for now the perfect test to identify bacterial superinfection in viral respiratory tract disease remains elusive, and the clinician must use multiple clues in assessing the need for, and duration of, antibiotics.