The expression of major histocompatibility complex (MHC) antigens on the surface of cultured human embryonic myoblasts was studied by fluorescence microscopy. Class I or II MHC antigens were detected by monoclonal antibodies (MoAb) recognizing monomorphic determinants on HLA-A, B and C (class I), or HLA-DP, DQ and DR (class II) and a secondary fluorescein-labelled sheep anti-mouse immunoglobulin (Ig) antibody. Myoblasts were simultaneously identified using a MoAb directed against myosin light chains 1 and 2 (MLC1 and MLC2) and a combination of biotin-labelled sheep anti-mouse Ig antibody and Texas Red labelled streptavidin. We found that myoblasts demonstrated only very weak expression of either class of MHC but that, in the presence of more than 100 units of gamma-interferon (gamma-IFN) for 56-72 h, both class I and II MHC antigen expression increased significantly. During this time, class I antigen increased more than class II and at lower gamma-IFN concentrations. The implications of these findings for myoblast transfer therapy in Duchenne muscular dystrophy patients is discussed.