Modern techniques of mechanical hemapheresis have made it possible to selectively remove vast quantities of lymphocytes and plasma immunoglobulins, and the concentration of these substances in donor blood can fall below the normal range. It is feared that this may lead to immunosuppression; a condition associated in some clinical settings with infections, malignancy and autoimmune diseases. Using primary immunodeficiency diseases and induced immunodeficiency states (for example, therapeutic lymphocytapheresis, chronic thoracic duct drainage and intestinal lymphangiectasia) as models to judge competency of the immune system, it can be predicted that body defense mechanisms can become defective when serum IgG levels are less than 200 mg/dl or the blood lymphocyte count is less than 1000/microliter. However, impaired immunologic function can occur in the presence of normal quantities of these substances in the blood stream; conditions that may be related either to imbalances of immune regulatory factors or to qualitative (rather than quantitative) abnormalities of the immune system. A number of investigators have documented the losses of lymphocytes and plasma immunoglobulins incurred by donors experiencing mechanical hemapheresis. In addition, both the immediate and long-term decreases in the concentration of these substances in donor blood have been reported. In summary, the immediate decreases in blood lymphocyte counts and serum immunoglobulin concentrations are of slight to moderate degree and are without known adverse effects. Less information is available regarding long-term alterations of the immune system, and little data have been collected from prospective studies in which large numbers of donors have been thoroughly evaluated by modern techniques. In general, results of many laboratory studies have been altered. However, these abnormalities have been transient for the most part, and it has been difficult to document clinically significant adverse effects. Thus, the quantities of blood lymphocytes and plasma immunoglobulins that can be removed from healthy donors without causing significant immediate or long-term harm is unknown. Bearing these limitations in mind, the following recommendations are suggested regarding the frequency of repeated mechanical plasma-and-cytapheresis. 1) The usual requirements for whole blood donation must be met if the frequency of mechanical hemapheresis does not exceed once every eight weeks.(ABSTRACT TRUNCATED AT 400 WORDS)