In 53 patients with progressive systemic sclerosis (PSS) the lymphocytotoxic activity of their serum was measured in a microlymphocytotoxicity assay. In 21 of the 53 patients the test reacted distinctly positively in the heterologous system, and in 9 of these 21 also in the autologous system. After preparation of the immunoglobulins from these positive sera, whole cytotoxic activity was detected only in the IgM fraction but not in the IgG fraction. When using prepared T lymphocytes as target cells in the microlymphocytotoxicity test, the cytotoxic activity of the positive PSS sera showed itself to be directed against this lymphocyte population. Further analysis using the Western-blot technique showed that the IgM autoantibody in PSS sera reacted with the cell surface of CD4+ lymphocytes. The cross reactivity with extractable nuclear antigens was rather improbable. These results suggest that lymphocytotoxic autoantibodies may play a role in immunological disturbances in PSS.