This study was aimed to investigate the role of bone marrow microenvironment in the regulation of activator protein 1 (AP-1) expression in multiple myeloma (MM) cells. The primary myeloma cells (CD138(+) cells) from 8 patients with MM were sorted by using immunomagnetic beads and were cocultured with osteoclasts in alpha-MEM supplemented with 10% fetal bovine serum, antibiotics, RNAKL (50 ng/ml) and macrophage colony-stimulating factor (25 ng/ml) for 10 to 14 days at 2.5 x 10(6) cells/ml. The expression levels of genes c-jun, junD fos and fosB were detected by real-time PCR. The results showed that the osteoclasts were observed after coculture of mononuclear cells in peripheral blood of MM patients with osteoclasts for 10 - 14 days. As compared with control (without coculture with osteoclasts), the viability of MM cells cocultured with osteoclasts obviously increased, the expression levels of c-jun, junD, fos and fosB decreased to 25.7% - 1.66%, 68.49% - 8.54%, 10.35% - 0.19% and 36.63% - 3.44% of the control respectively. It is concluded that the bone marrow microenvironment can inhibit the expression of c-jun, junD, fos and fosB promote myeloma cell proliferation and maintain cell survival.