We investigated the mechanisms of specific immune unresponsiveness to microfilarial antigens. The blood of patients with obvious Brugia malayi infections contains an adherent cell type that specifically suppresses reactions to microfilarial antigens but not to other antigens. In the absence of continued stimulation by parasite antigens, this suppressor cell loses its functional activity after overnight culture in vitro. Furthermore, serums from patients with and without microfilaremia contain factors that also suppress reactions to filarial antigens in vitro. These results suggest that immune unresponsiveness in human beings with patent filarial infections is due to active suppression of immune responses directed against the parasite and not to an intrinsic inability of infected patients to react to parasite antigens.