The proliferation and differentiation of multiple myeloma (MM) cells has been suggested to be induced by continuous stimulation of interleukin (IL)-6 in the bone marrow (BM) microenvironment. We investigated the production and gene expression of this cytokine in bone marrow mononuclear cells (BMMC) of 31 untreated patients with MM. The IL-6 gene was expressed in 20/31 patients in whom increased IL-6 production in vitro was observed, suggesting that IL-6 gene expression correlates with IL-6 production by BMMC. A significant correlation was found between the presence of bone lesions and IL-6 gene expression; however, the percentage of MM cells infiltrating the BM did not correlate with IL-6 gene expression. This IL-6 gene expression was assigned to adherent cells of the BM microenvironment. Furthermore, serial measurement of IL-6 gene expression along with the clinical course revealed increased expression of IL-6 gene during the progressive phase of MM and decreased expression after remission at the individual level. These results suggest that IL-6 gene expression in BMMC reflects disease severity in MM.