Monocyte derived cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), were determined in cell free plasma after stimulation of heparinized whole blood from chronic lymphocytic leukemia (CLL) patients with lipopolysaccharide (LPS) at 1 microgram/ml for 6 hr. Compared to control donors (390 U/ml), CLL patients in average had eight-fold lower levels of TNF bioactivity (50 U/ml). The depressed levels were observed over a wide range of LPS concentrations (0.01 to 10 micrograms/ml). Furthermore, after stimulation with S. aureus bacteria, CLL samples gave three-fold lower levels, as well. TNF levels were not decreased because of defective bioactivity of TNF, since strongly reduced levels of TNF protein were also detected in an immunoassay. Finally, interleukin-6 levels after LPS stimulation were decreased threefold. Flow cytometry analysis with CD14 antibodies demonstrated comparable numbers of monocytes for control donors and CLL patients (698 +/- 802 and 427 +/- 267, respectively). This suggests that deficient cytokine production was not due to a reduction in monocyte number, but rather to a functional impairment. The deficiency in cytokine production observed after ex vivo stimulation of whole blood from CLL patients suggests that in vivo during bacterial infection, CLL patients will exhibit an inappropriate response as well.