AbstractForty‐two patients with chronic lymphocytic leukemia (CLL) were studied for morphology of lymphocytes by light and electron microscopy (EM), in vitro responses of lymphocytes to a battery of physical and chemical agents, overall clinical status, immunologic status, course, and response to therapy. CLL lymphocytes could be classified by EM into four groups on the basis of cell size and nuclear contour and by light microscopy into two groups, small cells and large cells (lymphosarcoma cells). Patient survival did not vary with cell size or morphology as determined by light or electron microscopy. In vitro testing of CLL lymphocytes following exposure to x‐ray, PHA, DMSO 2 hr at 43°, prednisolone, glutaminase, and asparaginase permitted a separation of patients into categories of normal and abnormal in vitro responses. A normal in vitro response predicted a good response to therapy but an abnormal in vitro response did not preclude a good response to therapy. Following therapy, normalization of abnormal EM morphology and in vitro response was seen in some patients. Most patients tested had decreased serum immunoglobulins and abnormal PHA responses. There was a high incidence of infections and second neoplasms. Immunologic deficits could not be correlated with variations in lymphocyte morphology or in vitro resp