The present studies were designed to characterize the in vitro responsiveness of jird lymphocyte populations to fractionated Brugia pahangi antigens in the B. pahangi-jird model of filariasis. Proliferative responses to spleen and lymph node cells from normal, B. pahangi-immunized, and infected jirds to HPLC fractions of soluble and detergent extracted antigens were assayed. High molecular weight fractions of soluble B. pahangi were weakly mitogenic for normal lymph node, but not normal spleen cell populations. Lymphocytes from B. pahangi-immunized jirds responded to a wide range of fractions corresponding to antigens with molecular weights from less than 10 kd to greater than 300 kd. A shift in the reactivity of spleen cells from infected jirds to fractions of both soluble and detergent extracts was observed over the course of B. pahangi infection. Spleen cells from microfilaremic jirds consistently failed to respond to any of the fractions which significantly stimulated spleen cells from animals with prepatent infections. In contrast, lymph node cells from prepatent and microfilaremic jirds displayed similar profiles of antigenic reactivity. These results suggest that the development of patent infection leads to a complete down regulation of splenic, but not lymph node cellular reactivity to parasite antigen.