We have suggested a growth stimulatory role of lymphoma cells in culture by interleukin 6. To test the hypothesis that IL-6 may have a role in vivo, the plasma of lymphoma patients was assayed for the presence of IL-6 bioactivity. A significantly greater proportion of lymphoma patients had elevated IL-6 levels (23 of 40) compared to controls (3 of 35). In follow-up, eight of 15 patients with previously elevated levels returned with decreased or undetectable levels of IL-6 post radio- or chemotherapy. This response was seen primarily in those with intermediate or high grade lymphomas. In contrast no change in IL-6 levels was seen in patients with low grade lymphoma despite measurable reductions in tumor size in both groups.