Immunological abnormalities of an autoimmune nature often develop during acute primary human cytomegalovirus (HCMV) infection. IgM antibodies reacting with the membrane of uninfected human embryonic fibroblasts can be detected in most patients undergoing a primary HCMV infection. In this work, we have found that there is a common antigenic epitope shared by a cell membrane component of Mr 60K (mp60), which is recognized by IgM in sera from patients with primary HCMV infection, and a linear determinant in the C-terminal half of the HCMV assembly protein of Mr 38K (vp38), which is known to be one of the most IgM-reactive antigens of HCMV. While vp38 seems to contain other specific IgM-reactive regions, IgM reactivity to mp60 is due exclusively to this shared epitope. Furthermore, mp60 is found abundantly on the surface of human red blood cells, a possible explanation for the pathogenesis of the haemolytic anaemia that may appear during primary HCMV infection.