Fey RIII (CD16) expression of neutrophil granulocytes was measured in 156 patients by means of fluorescence-labeled antibodies with a flow cytometer. Results were compared with (1) 400-cell manual differential count; (2) left shift flagging on hematology analyzers; (3) absolute neutrophil count; and (4) acute-phase protein levels. Asynchrony was noted between neutrophil CD16 expression and microscopically defined neutrophil stage, particularly in heavily left-shifted samples, which made it impossible to reliably enumerate immature neutrophils on the basis of CD16 expression. According to receiver operating characteristics, the absolute count of CD16-negative neutrophils was highly discriminatory for detection of left shift, with an area under the curve (AUC) of 0.842 ± 0.03 (SE) and maximum efficiency of 81% ± 3%, but absolute neutrophil count was not significantly inferior (0.821 ± 0.03 and 76% ± 3%). STKS and SE9000 flagging demonstrated efficiency of 76% ± 3% and 81% ± 3%, respectively. For detection of acute-phase response, absolute neutrophil count (AUC, 0.836 ± 0.04; maximum efficiency, 80% ± 4%) outperformed both quantitative neutrophil CD16 expression (0.760 ± 0.05; 75% ± 4%) and absolute CD16-negative neutrophil count (0.757 ± 0.05; 71% ± 4%); absolute band count performed similarly (0.853 ± 0.04; 79% ± 4%) and showed high efficiency at high sensitivity and specificity. Efficiency of analyzer flagging for detection of acute-phase response was not superior to absolute neutrophil count (STKS, 77% ± 4%; SE9000, 78% ± 4%). In conclusion, the diagnostic value of measuring neutrophil CD16 expression was generally similar to that of less complicated analytes.