Hyaluronan (HA) is suggested to play a role in the pathophysiology of multiple myeloma. To further investigate the role of HA in this disease, we examined hyaluronan synthase (Has) gene expression and HA production in bone marrow mesenchymal progenitor cells (bmMPCs) derived from multiple myeloma patients. The relative abundance of mRNA for each HAS gene was determined using competitive reverse transcription-polymerase chain reaction (cRT-PCR), whereas HA production was detected by fluorophore-assisted carbohydrate electrophoresis (FACE). We determined the basal expression of Has isoforms in myeloma bmMPCs and then compared this expression with expression in healthy donor bmMPCs. Of the 3 Has isoforms, Has1 mRNA was expressed predominantly in myeloma bmMPCs, with expression 7.6-fold greater than Has2. Compared with normal bmMPCs, Has1 mRNA expression was 20-fold greater in myeloma bmMPCs. Normal bmMPCs predominantly expressed Has2 mRNA (8.2-fold greater than myeloma bmMPCs). Upon coculture of myeloma bmMPCs with plasma cells, Has1 transcript was strongly attenuated. FACE results show that myeloma bmMPCs synthesize 5.7-fold more HA than those from healthy donors. These data suggest that myeloma bmMPCs could be an important component of the myeloma pathophysiology in vivo by their increased expression of extracellular matrix (ECM) components relevant to plasma cell growth and survival.