Accessory function of monocytes for T-cell activation was studied in patients with systemic lupus erythematosus (SLE). Nylon column-purified T cells alone were not activated to proliferate by stimulation with concanavalin A (Con A), but the addition of dish-adherent monocytes restored the T-cell response in a dose-dependent manner (accessory function). This accessory function is mediated by HLA-DR-positive monocytes. This accessory function of monocytes was markedly impaired in SLE patients. The dysfunction of monocytes was marked in an active stage of SLE but not in an inactive stage of SLE. Furthermore, SLE T cells were not fully activated with Con A in the presence of normal monocytes, suggesting that both monocyte and T-cell functions were impaired in SLE patients. The dysfunction of SLE monocytes was due to neither the development of suppressor monocytes nor the overproduction of prostaglandins, because SLE monocytes did not suppress the accessory function of normal monocytes and indomethacin did not restore the dysfunction of SLE monocytes. The percentage of HLA-DR-positive cells in a monocyte population was markedly decreased in active SLE patients and moderately decreased in inactive SLE patients. Thus, the impairment of accessory function of monocytes in SLE patients seems to be derived from a decrease in HLA-DR-positive monocytes. These results suggest that the dysfunction of HLA-DR-positive monocytes plays an important role in the pathogenesis of SLE.