Plasma concentrations of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) were serially determined in 32 patients with acute myeloid leukemia who developed severe sepsis (n = 19) or septic shock (n = 13) during chemotherapy-induced leukocytopenia (< or = 1 x 10(9)/L). Starting within 2 h of fever onset, IL-6 levels rose significantly over baseline in both groups to markedly higher levels in patients with evolving septic shock (medians: 372 vs. 3671 pg/mL; P < .001). Simultaneously, sIL-6R significantly decreased to lower levels in shock patients than in septic patients without hypotension (53 vs. 93 ng/mL; P = .02). This pattern was maintained throughout the observation period of up to 6 days. In patients with fatal sepsis, peak IL-6 levels were significantly higher than in survivors (P < .001), whereas minimum sIL-6R levels were markedly lower (P = .003). The reciprocal changes in circulating IL-6 and sIL-6R suggest a role for sIL-6R in modulating the effects of IL-6 during evolving sepsis in leukocytopenic patients.