Lymphocytes obtained from CLL patients containing high and low peripheral lymphocyte cell counts were cultured in the absence and presence of increasing concentrations of phytohemagglutinin for periods of up to 2 h. Lymphocytes from patients with low cell counts (less than 50,000/mm3) were stimulated to incorporate 3H-uridine during the 1st h of culture by concentrations of PHA ranging from 1 to 32 microgram/ml. Under identical conditions, lymphocytes from patients with high cell count (greater than 50,000/mm3) were barely affected. During the 2nd h of culture the above concentrations stimulated to a lesser degree the former group of lymphocytes, whereas it inhibited incorporation by the latter group. The results obtained suggest a qualitative difference in the response of CLL lymphocytes to PHA in accordance with the progression of the disease.