Knowledge concerning leukocyte functions has increased enormously over the last two decades, largely because techniques have become available to assess them. It has provided insights into many disease entities, as well as on immunologic functioning as a whole. In addition to some classical clinical entities, such as severe combined immunodeficiency disease and chronic granulomatous disease, new entities have been discovered and described, in which subtle disturbances in white blood cell function are sufficient to cause disease. Furthermore, much has been learned about the effect of drugs and disease conditions on leukocyte functions. This review is not intended as a comprehensive description of white blood cell function testing, rather, it is meant to provide a practical guide for clinical laboratories. Therefore only those functional tests are presented which have a direct impact on patient management. These are primarily those functional derangements in white cells which either define a disease entity or without which a diagnosis cannot be made. Granulocytes, monocytes, and lymphocytes will be discussed separately. A short review of their physiology and function is presented to provide a context for the further discussion of their dysfunctions. This discussion of dysfunction and the techniques for laboratory testing thereof includes the evaluation of diagnostic usefulness and implications for patient management. Clinically, the most important granulocyte defects involve chemotaxis, respiratory burst, and intracellular microbial killing. Defects of granulocyte chemotaxis define the lazy leukocyte syndrome, Job's syndrome, and a series of relatively rare idiopathic neutrophil disorders. In addition, chemotaxis is a relatively easily measured sign of actin dysfunction. Defective generation of the respiratory burst with consequent impaired microbial killing defines chronic granulomatous disease and its variants as well as glutathione peroxidase deficiency. The most reliable clinical laboratory testing of granulocyte chemotaxis is performed by using granulocyte migration in response to a chemoattractant, either across a filter or in agarose. For clinical testing of respiratory burst, nitroblue tetrazolium (NBT) reduction is simple, quantitative, and has recently been adapted to automated measurement. Direct measurement of microbial killing is generally not indicated, since clinically important defects are recognized by measurement of respiratory burst generation. Although the monocyte's functions are numerous, they are somewhat less well characterized than those of granulocytes and lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)