Parasitic nematodes are constantly exposed to the immune effector mechanisms of their hosts. One strategy of the worms to cope with these defence reactions is the secretion of modulatory proteins that down-regulate cell-mediated immune responses. We analysed the proliferation of mesenteric lymph node cells of mice infected with Heligmosomoides polygyrus and showed that cellular proliferation was strongly suppressed in the chronic phase of infection. To identify proteins of H. polygyrus that are involved in parasite-induced immunomodulation, worm extract and culture supernatant of adult H. polygyrus were fractionated by gel chromatography and activity of each fraction was determined. One of the fractions (fraction 9) of worm extract as well as worm secretory products inhibited the antigen-specific cellular proliferation by about 40%. This reduced cellular reactivity coincided with a down-regulation of inducible nitric oxide production of mouse macrophages by 57%. Furthermore, fraction 9 contained antigens that were recognized by IgE antibodies of H. polygyrus-infected mice and induced degranulation of an IgE-sensitized basophil cell line. Single proteins of fraction 9 were analysed by mass spectrometry. These data suggest that antigens that are recognised by IgE antibodies might play an important role in immunomodulation exerted by nematode infections.