Suppressor cell activity (SCA) was studied in twenty-eight patients with insulin-dependent diabetes mellitus (IDDM), both newly diagnosed and of longer standing. Suppressive effect of peripheral blood lymphocytes from the patients was tested after 48 hr of incubation with concanavalin A followed by inactivation. Suppression was measured as the ability of the lymphocytes to inhibit 3H-thymidine incorporation in concanavalin A-stimulated normal donor lymphocytes. SCA was expressed in relation to the activity of peripheral blood lymphocytes from simultaneously investigated healthy control individuals. The main findings were: (1) SCA was significantly depressed in newly diagnosed diabetics and (2) newly diagnosed patients displayed significantly lower SCA than did patients with duration of disease between 2 and 8 months and between 5 and 8 years, who had suppressor cell activities not significantly different from healthy individuals. Earlier studies have pointed to the significance of immune reactions in diabetogenesis. On this basis, and on the strength of our present findings, it is suggested that an impaired SCA, causing a decreased inhibition of aggressive lymphocytes, may be implicated in the pathogenesis of insulin-dependent diabetes mellitus.