Patent filarial infection is associated with the downregulation of parasite-specific immune reactivity. In the present study, the relationship between in vitro parasite antigen-specific humoral and cellular immune responsiveness was investigated in Brugia pahangi-infected jirds and in jirds immunized with soluble antigens. Spleen cells from B. pahangi-immunized jirds or from jirds with prepatent infections mounted significant in vitro proliferative and antibody responses to B. pahangi. The antigen concentration which elicited optimal antibody production was 10- to 10,000-fold lower than that required to stimulate optimal blastogenesis. Lymph node cells from both immunized and infected jirds consistently produced lower levels of parasite-specific antibody than spleen cells, yet generated higher proliferative responses to filarial antigen. A dissociation between in vitro antibody production and proliferation was also observed in experiments with spleen cells from microfilaremic jirds; spleen cells from patent animals did not proliferate when stimulated with B. pahangi antigen, but did produce significant levels of parasite-specific antibody. Depletion of adherent or histamine receptor-bearing cells restored the proliferative reactivity of spleen cells from microfilaremic jirds, but had limited effects on antibody production. In admixture experiments, spleen cells from microfilaremic animals suppressed the proliferative responsiveness of cells from keyhole limpet hemocyanin (KLH)-immunized jirds to KLH by 38%, but had no effect on KLH-specific antibody production. The present results support the hypothesis that parasite-specific cellular and humoral reactivity are differentially regulated in experimental filariasis.