Proliferative response of peripheral blood mononuclear cells to phitohemoagglutinin and anti-CD3 mitogenic monoclonal antibodies (MoAbs) of the IgG2a (OKT3) and IgG1 (PanT2, CLB T3/4.1) isotypes was studied in 39 patients with systemic sclerosis (SSc) and in 82 control subjects. The effect of IL-2 on this response was also investigated. No difference in the response to PHA and to IgG2a anti-CD3 MoAb OKT3 was seen between scleroderma patients and controls. Both the patient and control groups contained responders and non-responders to IgG1 anti-CD3 MoAbs. The percentage of non-responders was significantly higher in scleroderma patients than in controls. When purified lymphocytes from non-responder scleroderma patients were cultured with monocytes from control responders, proliferative response to IgG1 MoAbs was restored. Our results show that monocytes from patients with systemic sclerosis bear a defect leading to IgG1 unresponsiveness by T lymphocytes.