Beta 2-Microglobulin (beta 2 m) dissociated from surface HLA class I complex following exposure of cells to low pH and was detected in supernatant by radioimmunoprecipitation with specific monoclonal antibodies (mAbs). As the concn of beta 2m in supernatant increased, the binding of mAbs, specific for HLA class I heavy chains associated with beta 2m, to the cell surface declined. Binding of mAb specific for free HLA class I heavy chain to the cell surface increased after acid treatment. Reassociation with exogenous beta 2m confirmed increase in the number of free HLA class I heavy chains on surface of the cells after their exposure to low pH and also at least partially restored the reactivity with mAbs specific to HLA class I heavy chains associated with beta 2m. Dissociation of beta 2m from CD1 complex following acid treatment was also accompanied with the changes in antigenicity of cell surface CD1 molecules.