The hematologic profiles of 1000 newborns were prospectively examined to identify infants with neutropenia (N = 170) according to the system of Manroe et al. (J Pediatr 1979;95:89-98) and to evaluate a hematologic scoring system (Rodwell et al. J Pediatr 1988;112:761-7) as a screening test for sepsis. Neutropenia was more commonly of noninfectious than infectious origin (83.5% vs. 16.5%; P < 0.001). On the initial test a positive screen (scores > or = 3) identified 26 of 28 infants with sepsis or probable infection (sensitivity 93%; specificity 82%; positive and negative predictive values 50 and 98%, respectively). Corresponding values for an elevated immature:total neutrophil ratio were 100, 75, 43 and 100%. Overall mortality with neutropenia was 15% and was higher with an infectious than a noninfectious etiology (39% vs. 11%, P < 0.001) despite early antibiotic therapy. The combination of a neutrophil count < or = 500/mm3 and scores > or = 3 or an elevated immature:total neutrophil ratio identified a poor prognostic group: 67% (8 of 12) and 70% (7 of 10) infants, respectively, with these findings died, 6 in the infected group. The hematologic scoring system or immature:total neutrophil ratio in combination with the degree of neutropenia provides valuable diagnostic and prognostic information which could be applied to identification of possible candidates for granulocyte transfusions or other experimental treatments.