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Mycloma cells absolutely require interleukin-6 (IL-6) for growing in vivo in patients with multiple mycloma and exogenous IL-6-dependentmycloma cell lines have been reproducibly obtained. In this study we show a dramatic up-regulation of the IL-6 receptor (gp80 chain) gene expression in mycloma cell lines following the removal of exogenous IL-6. Such a regulation was also known to occur in IL-6-deprived mycloma cells in vivo in three patients who were treated with optimal doses of anti-IL-6 monoclonal antibodies. The direct effect of IL-6 on IL-6 receptor gene expression in mycloma cells was further confirmed by adding IL-6 to an autonomously growing mycloma cell line.