The growth characteristics of myeloma cells are in striking contrast with those of normal, non-dividing end-stage plasma cells. Interleukin 6 (IL-6) has been shown to be a key growth factor for myeloma cells, however, IL-6 only acts as a differentiation factor for normal B cells. Wc have hypothesized that the differential response of myeloma cells to IL-6 may either result from altered IL-6 signal transduction and or from inappropriate IL-6-induced expression of genes whose products are key for continued tumor cell growth. To test this hypothesis, we have employed two experimental strategies. First, we are using cDNA array screening technology to identify IL-6 responsive genes in myeloma cells. Second. we are using a chimeric receptor approach to identify the regions of gp130, the signal transducing component of the IL-6 receptor, that are essential for myeloma cell proliferation. To this end, we have utilized a panel of IL-6 growth-responsive myeloma cell lines and a panel of mutant gp130 chimeric receptors. This combined approach has the potential to assess the relative importance of several signalling events in myeloma cell growth control and identify IL-6 responsive genes in this malignancy.