A simple diagnostic test for sepsis will be extremely useful in the clinical assessment of neonates, whose immunological immaturity leads to difficulty in determining the presence of infection. The aim of this study was to determine whether altered expression of CD11b (Mac-1 or CR3) on granulocytes can serve as a marker for sepsis, thereby identifying infants in need of critical therapy and sparing infants who are not at risk a costly stream of tests, procedures and medications. 0.1 ml whole blood samples were obtained from newborns admitted to the Neonatal Intensive Care Unit to rule out sepsis. Samples were diluted with 2.5 ml staining media, and stained with Phycoerythrin-conjugated CD11b monoclonal antibody and Fluorescein-conjugated CD15 monoclonal antibody. CD11b expression on neutrophils was then determined by flow cytometry. Blood was simultaneously sent for routine bacterial culture, complete blood count (CBC) and C-reactive protein (CRP) determination by the hospital's diagnostic facility. Results of bacterial cultures, CBC and CRP were obtained 5 - 7 days later, and were correlated with the previously determined (and thus blinded) neutrophil CD11b expression. Results from 106 subjects demonstrated high median neutrophil CD11b in all infants in which a positive culture was obtained. High levels of CD11b were associated with increased CRP. Neonates with no elevation in CRP, negative bacterial cultures and no other clinical signs of sepsis had low levels of CD11b expression(r=.81, p<.001). Both CD11b and CRP were elevated in 100% of subjects with positive bacterial cultures. However, CD11b was elevated on the first hospital day in 90% of cases, whereas CRP was elevated on the first hospital day in 30% of cases. These results strongly suggest that elevated CD11b indicates infection in neonates. This elevation is likely to occur close to the time of pathogen exposure, whereas CRP elevation appears to occur hours later, requiring serial CRP determinations over a number of days to obtain confidence in the result. Thus, the ease, speed and small amount of blood required to perform this test will make the CD11b assay a convenient diagnostic tool for infants at risk for sepsis.