Humoral suppressive factors were identified in the plasma of 13 of 14 patients with schistosomiasis mansoni. These factors suppressed lymphocyte proliferative responses to parasite antigens but did not affect lymphocyte responses to either nonparasite antigens or mitogens. Furthermore, they had no inhibitory effect on proliferative responses of lymphocytes of normal, noninfected individuals. Three patients studied sequentially before and after therapy with niridazole developed positive lymphocyte responses to parasite antigens within the first month of treatment, but this enhanced responsiveness was not accompanied by clearance of these humoral suppressive elements, which persisted in the patients' plasmas. Such suppressive factors which are specific for responses to parasite antigens probably form one of the mechanisms which determine the state of partial immunosuppression found in patients with chronic schistosome infection.