Immunophenotyping of leukocytes for nonmalignant conditions uses the power of multiparameter flow cytometry to count specific lymphocyte populations and evaluate the presence or absence of particular cell surface markers. Its main clinical indications, and the focus of this chapter, are enumeration of CD4 T-cell counts and activation markers on T cells in human immunodeficiency virus (HIV) infection, immunophenotypic characterization of primary immunodeficiency disorders and immune-mediated diseases, and the study of immune reconstitution following stem cell transplantation (SCT). Immunophenotyping has advanced our understanding of many immunologic disorders, which in turn have stimulated new developments in the field of flow cytometry, such as quantitative flow cytometry and single-platform technology. Semin Hematol 38:100-110. This is a US government work. There are no restrictions on its use.