A group of Venezuelan patients with SLE showed an increased proportion of responders to Leu-4, an anti-CD3 MoAb of the IgG1 class, compared with ethnically matched non-SLE patients and healthy controls. The rate of proliferative responses or IL-2 production induced by MoAb Leu-4, and the helper effect of macrophages from Leu-4 responders on T cells from a third-party donor were comparable in patients and controls. No significant differences in the binding of murine IgG1 molecules by macrophages from SLE patients and controls were observed. The proportion of monocytes/macrophages expressing FcγRI was significantly higher in SLE patients. However, the expression of FcRII, the type capable of supporting Leu-4-mediated responses, and of FcγRIII was comparable in monocytes from SLE patients and controls. Our results suggest that Venezuelan patients with SLE may have a genetic predisposition for the expression of the phenotypic variant of FcγRII capable of binding murine IgG1 molecules.