Human peripheral blood lymphocytes from patients with chronic Schistosoma mansoni infection were exposed to concanavalin A (Con A), soluble schistosome egg antigenic preparation (SEA), or soluble adult worm antigenic preparation (SWAP). They were then evaluated for their ability to suppress the phytohemagglutinin response of autologous cells. Significant suppression was reliably obtained by Con A pretreatment of the cells of 15 of 17 patients (88%). Pre-exposure of patient's cells to SEA and SWAP in medium supplemented with normal human serum (NHS) resulted in significant suppression being expressed by 36% and 39% of the patients, respectively. The ability to express suppressor activity in these circumstances did not appear to correlate with the intensity of the patient's S. mansoni infection, or the clinical state of the patient's disease. The capacity to generate schistosomal antigen-induced suppressor activity increased sharply during the second decade of life, in general, correlating with increased duration of infection. Preliminary studies have indicated that the ability to generate schistosome antigen-induced suppressor activity was greatly increased when the cells were exposed to the antigens in the presence of “suppressive” sera from a patient with chronic S. mansoni infection rather than NHS. This information suggests a synergistic relationship, involving antigenic exposure of both the cells and sera of certain chronic patients, which assists in the induction of suppressor activity. The immunoregulatory responses observed could be important in the establishment of a stable chronic infection state by modulating the extent of egg-induced granuloma formation and preventing rejection of the adult worm.