The in vitro response of lymphocytes from patients with chronic lymphocytic leukemia (CLL) to pokeweed mitogen (PWM) was diminished and/or delayed. Electron microscopy of PWM stimulated CLL lymphocytes revealed both PHA-type blast cells and plasmacytoid cells. Some PHA-type blast cells were indistinguishable from corresponding normal cells. However, many transformed cells had a reduced cell, cytoplasmic, and nuclear area in comparison to transformed lymphocytes from normal individuals. In 7- and 9-day cultures, 5-10% of the cells present were plasmacytoid. No ultrastructural differences were observed between the plasmacytoid cells in PWM stimulated cultures of normal and CLL lymphocytes. The findings support the concept that the circulating lymphocyte population in CLL is comprised predominantly of abnormal cells, in addition to a small number of normal T and B lymphocytes.