Abstract The role of cytokines in the control of beta-2 microglobulin release from various haemopoietic cells was studied in vitro. Cell types investigated were resting cells or blasts of the T Cell, B cell or monocyte-macrophage lineage. Mediators used in these experiments were r-IFN-α 2c, r-IFN-γ, r-TNF-α, r-TNF-ß, r-IL 1, r-IL 2 and r-GM-CSF. Nanogram amounts of some of these mediators strongly affected beta-2 microglobulin release in vitro. r-IFN-γ, r-IFN-α 2c and r-IL 2 strongly enhanced and r-TNF-α and r-TNF-ß occasionally increased shedding of beta-2 microglobulin. r-IL 1 and high concentrations of r-IFN-α 2c were inhibitory, whereas r-GM-CSF was ineffective. The impact of antigenic stimulation on beta-2 microglobulin release in mixed lymphocyte culture (MLC) was also studied. Stimulation with alloantigens in MLC greatly enhanced beta-2 microglobulin shedding, and this enhancement could be inhibited by a monoclonal antibody neutralizing human IFN-γ. Among the various cell types studied, macrophages derived from peripheral blood monocytes were most susceptible to cytokine-induced alterations of beta-2 microglobulin shedding. From these data, we conclude that cytokines not only control the static expression of beta-2 microglobulin on the surface of haemopoietic cells but also largely affect their shedding.