Two lines of Heligmosomoides polygyrus, QN and QA, were selected by passage, respectively, through naive and immune Quackenbush (Q) mice and their biology and capacity to induce immune responses in homologous Q and heterologous low- (SL) and high-responder (RH) mice were assessed. QA H. polygyrus survived the impact of otherwise protective immunity in Q mice better than did QN parasites, especially after a secondary infection. The enhanced survival of QA parasites was observed also in SL but not in RH mice. Infections with QA phenotypes induced a reduced antibody response and lower eosinophilia compared to QN parasites in Q mice. The total numbers of nucleated cells in the mesenteric lymph node (MLN) and spleen increased to different extents according to the genotype of the mice and the phenotype of parasite used: the increase was most profound in RH, least in SL and intermediate in Q mice; QN induced more lymphocytosis in the MLN and spleen than did QA parasite phenotypes. B cells from MLN and spleen, stained with fluorochrome-conjugated antibody against mouse Ig, showed increased intensity of fluorescence in the flow cytometric assay after infection with H. polygyrus, but to different degrees: the intensity increased most in RH and least in SL mice; more in Q mice infected with QN than with QA H. polygyrus. These results suggest that adaptation of parasites to immunity of the host is associated with reduction of their immunogenicity and is specific to the immune status and genotype of the host to which the parasites have become adapted.