Antigens from Heligmosomoides polygyrus, which had been passaged selectively for over 40 generations through naive (Hpn) and immune (Hpa) mice, were extracted as whole worm (WWA) and membrane bound antigens (MBA), soluble adult worm homogenates (AWH), and excretory/secretory (ES) products. The antigen complexes were separated by SDS-PAGE, and 2-dimensional electrophoresis and assayed by western blot. Qualitative and quantitative differences were observed between profiles and antigenic reactivity of the constituents from selected parasites, which reflected their genetic heterogeneity. The survival of Hpa parasite phenotypes was improved compared with that of their Hpn counterparts in homologous strains of immunized mice but this did not correlate strongly with the antigenic differences observed. Three small molecules at 18, 21 and 23 kDa, respectively, dominated the somatic and ES components of all worms but they were of low immunogenicity during natural infection in mice and after vaccination in rabbits; and their role in immunomodulation is discussed.