Minimizing variables of animal handling and sample processing are essential to collection of valid hematologic data from mice. When analyzing hematologic data from mice, concurrent controls are used as the primary comparison for interpretation of treatment-related changes. Comparison to reference intervals may be also useful to put hematologic changes in perspective. Relative (percent) white blood cell counts and reticulocyte counts are not relevant parameters; rather, absolute counts are reported and interpreted. Major hematologic characteristics of mice, compared to humans, include smaller and more numerous red cells and shorter half-life of red cells; more circulating polychromatophils and reticulocytes; lower neutrophil counts and higher lymphocyte counts; high percentage of lymphocytes in bone marrow; increased dependence on splenic hematopoiesis in health and during accelerated hematopoiesis; shorter platelet life span; and more numerous platelets. Unlike humans, lymphocyte counts of mice are commonly increased in inflammatory conditions. Research on murine hematology is crucial to one's understanding of the biology of hematology and hematopoiesis. The comparative hematology of the mouse furthers the understanding of human hematology. Although there are important interspecies differences between murine and human hematology, these differences are far outweighed by similarities in these hematologic systems.