The proliferative effect of tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin on B cells from patients with B-chronic lymphocytic leukemia (B-CLL) was studied. Fresh purified B-CLL lymphocytes showed no proliferative response to either recombinant (r) TNF-alpha or r-lymphotoxin. However, after "in vitro" activation of B-CLL lymphocytes for 2 days with Staphylococcus aureus Cowan 1 (SAC), four of seven patients showed enhanced blastogenic response in the presence of either rTNF-alpha or r-lymphotoxin. We also found that the proliferative response of SAC-activated B-CLL lymphocytes to the two cytokines was independent of that found in the presence of interleukin-2. These results demonstrate that TNF-alpha and lymphotoxin can heterogeneously support the proliferation of in vitro activated B cells from B-CLL patients and may reflect the biological heterogeneity of B-CLL disease.