The increasing availability of reagents and technologies has resulted in the widespread use of immunophenotyping to define and assess the course of pathologic disorders involving lymphoid cells. The diversity of markers and of the disorders concerned has complicated the application of the technique. This paper reviews lymphocyte differentiation antigens, the technologies available to study them and possible applications in immunopathology. Four major disease groups are discussed: spontaneous immunodeficiencies, iatrogenic immunodeficiencies, auto-immune disorders and lymphoproliferative diseases. The importance of sequential explorations is stressed, where the abnormalities observed are analysed in the dynamic context of the disease and its therapy.