Parasitological and immunological parameters of experimental or naturally acquired infections with Haemonchus contortus were compared in St. Croix and Dorset lambs. In experimental infections, St. Croix lambs developed significantly greater levels of resistance to H. contortus, following primary exposure, as compared with Dorset lambs. This resistance was influenced both by age and by prior exposure to parasites. In grazing experiments on H. contortus-infected pasture, St. Croix lambs shed significantly fewer eggs as early as 5 weeks following initial exposure. Further, St. Croix lambs had more than 99% fewer worms in the abomasum at necropsy compared with age-matched Dorset lambs. Lymphoproliferative assays using peripheral blood mononuclear cells and antigen-specific serological tests demonstrated only minor differences in immune responsiveness between the two breeds despite the dramatic parasitological differences. Similarly, abomasal mucus from both breeds had elevated levels of parasite-specific antibodies and contained substances mediating larval paralysis. In contrast, St. Croix lambs which had become resistant to nematode infection had dramatically higher numbers of globule leukocytes in the abomasal mucosa compared with Dorset lambs.