The Coulter S-Plus IV separates leukocytes in peripheral blood by volume analysis into granulocytes, lymphocytes, and mononuclear cell fractions, the so-called three-part differential (3PD). White blood cell (WBC) counts, hemoglobin concentrations, platelet counts, 3PDs, and histograms were compared with smear differentials on 3,861 samples, including samples from oncology patients, to determine the predictive value of the Coulter parameters in detecting smear abnormalities. Results showed good correlation between the 3PD and smear differential for granulocytes and lymphocytes (correlation coefficients were 0.883 and 0.868, respectively) and poor correlation for mononuclear cells (0.492). No histogram region flag indicators were observed in the following samples: 15 of 40 samples with greater than or 1% blasts; 105 of 183 with greater than or 1 nucleated red blood cell (NRBC) per 100 WBCs; 65 of 113 with monocytosis greater than 1,600/microL (1.6 X 10(9)/L); 425 of 548 with greater than 2,000 bands/microL (2.0 X 10(9)/L); 84 of 112 with eosinophilia greater than 600/microL (0.6 X 10(9)L); and 88 of 149 with greater than 2% immature granulocytes. All samples with greater than 5% blasts were indicated by region flags and abnormal histograms. Oncology patient data were analyzed, yielding similar results. The authors established guidelines for using the Coulter 3PD data in their tertiary care laboratory to select samples that require smear evaluation.