Treatment with cyclophosphamide alone or in combination with methotrexate can cause considerable depression of the in vitro P.H.A.-lymphocyte transformation. This means that the longliving lymphocytes are affected. As a rule this depression is reflected by a fall of the number of circulating lymphocytes. One the other hand no influence on the content of the immunoglobulins has been found. Therefore it seems that the short living lymphocytes populating the germinal centres of the lymph glands remain functionally intact. More drastic forms of cytostatic therapy may have more serious consequences. Impaired lymphocyte transformation is the rule in the cachectic stage of malignant disease. It was also observed in several untreated cases of bronchus carcinoma.