Expression of class II major histocompatibility (MHC) antigens by peripheral blood monocytes from 12 patients with Hodgkin's disease (HD) were studied employing antiserum and complement-mediated cytotoxicity. Overall, the expression of class II MHC antigens was significantly decreased on HD monocytes (cytotoxicity index [C.I.] = 60.2 +/- 5.8% vs 77.6 +/- 2.8%, P less than .02). This decrease was most marked in patients with more severe disease. In fact, mean alloantigen expression for patients with advanced stages of disease was 58% of that observed in controls. The number of human lymphocyte antigen (HLA)-DR antigenic sites per cell was also reduced as determined by monoclonal anti-DR antibody and FACS analysis. There was 38% more HLA-DR per cell in normal controls than in moderately advanced Hodgkin's patients. Class II MHC antigen expression on HD monocytes were increased partially by an IFN-gamma containing concanavalin A-stimulated human mononuclear cell culture supernatants (Con A sup), although remaining subnormal. When monocytes were cultured with Con A sup and indomethacin, alloantigen expression was increased in HD and control monocytes, but indomethacin failed to normalize class II MHC antigen expression on HD monocytes (C.I. = 72.3 +/- 4.7% vs 90.2 +/- 1.8%, P less than .01). We conclude that PGE accounts only inpart for the decreased alloantigen expression by HD monocytes. Interleukin (IL) 1 production by patients' monocytes was not reduced as compared to normals and therefore does not contribute to the decreased MHC II antigen expression. Decreases in alloantigen expression may be an important determinant of the T cell-mediated immune abnormalities in Hodgkin's disease.