Autoantibodies reacting with the cytoplasm of granulocytes and monocytes (anticytoplasmic antibodies [ACPAs]) were found in 42 of 45 patients with active Wegener's granulomatosis (WG) (sensitivity, 93%). Specificity was tested in selected groups of patients with closely related diseases. Of 58 patients without a diagnosis of WG, 2 had ACPAs (specificity, 97%). The significance of ACPA titration for assessing or predicting disease activity was evaluated in a 16-month prospective study of 35 patients with WG. Seventeen relapses were observed and all were preceded by a significant rise of the ACPA titer. Anticytoplasmic antibodies are a specific and sensitive marker for active WG; a rising titer is a sensitive marker for the development of a relapse.