The clinical use of the proposed performance standards for differential leukocyte counts is determined by multiple factors. Their use must be considered according to the specific use of the differential count, the sources of variability in differential counting, the relation between specific use and sources of variability, the role of analytic errors in the detection of nonspecific changes, the use of qualitative vs quantitative data, the sensitivity and specificity of the routine eye count, the role of disease or specific cell prevalence in determination of predictive value, the effect on use of automated instruments for screening, and whether abnormal specimen flagging can be done. The routine eye-count differential method, as performed by a well-trained technologist or technician, seems to lack both sensitivity and specificity. Because of the magnitude of technique- and method-related and biologic sources of variability, the 100- or 200-cell eye-count differential method is not a good screening method for detection of hematologic illnesses, particularly those that are uncommon. The automated differential leukocyte instruments address many of the technique- and method-related errors and are thus able to equal or exceed the performance of the routine eye-count differential method.