Immunosuppressive factors were evidenced in cell-free supernatant of S. mansoni schistosomes culture and incubation products of the parasite. Both parasitic materials decreased tritiated thymidine and leucine uptake in normal spleen cells from CBA mouse and Fischer rats and in peripheral human blood lymphocytes stimulated either by non specific mitogens (PHA, ConA, or LPS) or by allogeneic cells. The suppressive factor(s) was (were) heat-resistant, dialyzable and of molecular weight 500-1,000. The inhibition of lymphocyte proliferation was not due to cytotoxic or cytostatic activity on lymphoid cells, nor did the parasitic reagents interfere with the binding of fluorescein-labelled ConA. The suppressive activity was also demonstrated in the serum from rats infected for 4 weeks by S. mansoni and in the dialyzable fraction of it. This suggests the release by the parasite in vitro as well as in vivo of inhibitory factor(s) decreasing lymphocyte proliferation and brings therefore a new light on the machanism of immune deficiency in parasitic infections.