Abstract: Aberrant expression of genes regulating apoptosis/survival seems to be essential in the stepwise development of human multiple myeloma (MM). In this paper we have compared the expression of bcl‐2 family pro‐ and anti‐apoptotic genes in MM cell lines, primary MM cells and normal plasma cells. The Bcl‐2, Mcl‐1, Bcl‐xL/S, Bcl‐w, Bax, Bak, and Bad were shown to be expressed in both malignant and non‐neoplastic, normal plasma cells. Quantitative analysis revealed that the malignant phenotype seemed to correlate with an elevated expression of Mcl‐1, a decreased expression of Bax and, to a lesser extent, an increased Bcl‐2/Bax expression ratio. The possible influence of interleukin‐6 (IL‐6) in regulating the expression of the bcl‐2‐related genes was also examined. Using the IL‐6‐dependent MM cell lines U‐1958 and U‐266–1970 it was clearly shown that IL‐6 deprivation induced cell cycle arrest in both cell lines, whereas apoptosis was only detected in the U‐1958 cells. Furthermore, the anti‐apoptotic proteins Bcl‐2, Mcl‐1 and Bcl‐xL were down‐regulated, while the expression of the pro‐apoptotic Bax protein was increased. To conclude, we suggest that the expression pattern of the Bcl‐2 family of proteins separates the malignant phenotype of MM from normal plasma cells, and that the protecting effect of IL‐6 may be conducted via an altered balance between these proteins.