Although an autocrine growth mechanism through interleukin 6 has been advocated in human myeloma cells, reports of IL-6 production by cells from established myeloma cell lines are rare. In the present study, we examined whether or not a minute amount of interleukin 6 is produced in 4 human myeloma cell lines. IL-6 production was not detected in any of the 4 lines by enzyme immunoassay, bioassay with two interleukin 6-dependent murine hybridoma cell lines and Northern hybridization. However, we detected interleukin 6 mRNA in one (U266) of the 4 lines by the reverse transcriptase-polymerase chain reaction. Nevertheless, the proliferation of all 4 lines was not inhibited by an anti-interleukin 6 antibody. These results suggest that autocrine stimulation by interleukin 6 is not involved in the majority of human myeloma cell lines.