The nature of the mononuclear suppressor cell and the fraction of crude soluble egg antigen (SEA) capable of activating antigen-specific suppressor cells were studied in 32 Egyptian children infected with schistosomiasis mansoni. Crude SEA was fractionated on Con A Sepharose, and the unbound and bound material (eluted with alpha-methyl-D-mannoside) was recovered for use in the generation of suppressor cells by the use of a co-culture technique. The glycoprotein fraction was further purified by DEAE cellulose chromatography to isolate the major serologic antigen (MSA-1). We found that both the crude SEA and the "protein" fraction (nonadherent to Con A Sepharose) of SEA was capable of inducing antigen-specific suppressor cell activity in a dose-dependent manner. The glycoprotein fraction of SEA (including MSA-1) was responsible for inducing nonspecific suppression. The antigen-specific suppressor cell was characterized in terms of its adherence properties of plastic and the presence of a receptor for sheep erythrocytes (E). The nonadherent, E-rosette-positive mononuclear cells were found to be activated by the crude SEA, and the "protein" fraction of SEA was found to exert an antigen-specific suppressor influence. Clinically, suppressor cell activity was found to be statistically greater in patients with a high intensity of infection compared to those with a low intensity of infection, but it was not different in patients with regard to the presence or absence of organomegaly. These results provide further information on one of the immunoregulatory mechanisms operative in human S. mansoni infection and on the nature of the antigen(s) that activates this response during the course of infection.