Mitogen-induced Ts cell activity and (DR) expression on monocytes have recently been shown to be reduced in patients with multiple sclerosis (MS). In our study, T cells were cultured with autologous monocytes in the presence of Con A for 6 days (primary cultures). At the end of the culture T cells were isolated and were 1) tested for surface DR expression and 2) treated with mitomycin C and placed in a secondary culture of allogeneic responder cells and Con A, to test their suppressor function. Treatment of monocytes of the primary culture with an anti-HLA-DR antibody abolished the expression of DR Ag on the T cells as well as their ability to function as Ts cells in the secondary culture. Monocytes from patients with active MS expressed low levels of surface DR Ag and induced reduced amounts of DR Ag on the surface of autologous T cells in primary cultures, which in turn expressed deficient suppressor function when placed in secondary cultures. In contrast, monocytes obtained from patients with inactive disease expressed higher levels of DR and induced higher amounts of DR Ag on autologous T cells, which expressed normal suppressor function. We conclude that the deficient expression of DR Ag on MS monocytes causes reduced suppressor function in activated autologous T cells and may be a primary abnormality in the immunopathogenesis of MS.