Objectives: An automated complete blood cell count (hematology) analyzer cannot measure the white blood cell (WBC)differential of some patient sample, notably those of chemotherapy patients. This is often due to the presence of atypicalcells in the sample or matrix changes caused by drugs. A technique to use isotonic sodium chloride solution (0.9% saline) asa replacement for plasma has previously been described. The aim of this study was to evaluate to use of saline replacementas a means to resolve the matrix interference effect and achieve a reliable WBC differential count for chemotherapy patients. Methods: Samples of 29 chemotherapy patients whose WBC differential count could not be calculated using a Beck man Coulter LH-780 hematology autoanalyzer (Beckman Coulter, Inc., Brea, CA, USA) were evaluated. A peripheralblood smear was performed and the saline replacement technique was applied and the samples were then re-analyzedusing the same autoanalyzer. The WBC count and differential count of WBC of a peripheral smear and a saline-replace ment sample were compared. Results: There was no statistically significant difference between the peripheral blood smear and saline replacementautoanalyzer measurements of the WBC differential count and percent of WBC. Strong relationships in WBC (r=0.99),neutrophil (r=0.98), lymphocyte (r=0.98), monocyte (r=0.91), and eosinophil (r=0.77) counts were observed in a com parison of the peripheral blood smear and saline replacement measurements. Conclusion: A saline replacement technique may be a practical solution to resolve the difficulty of the matrix interfer ence effect seen in chemotherapy patient samples and provide a WBC differential count.