Partially purified low molecular weight antigens obtained by gel filtration of whole worm homogenates or total adult excretory–secretory (ES) products were tested in a vaccination experiment to determine their ability to induce protective immunity against Haemonchus contortus in sheep. Sheep were challenged with 20000 infective 3rd-stage larvae. One animal in the low molecular weight vaccinated group showed no protection against H. contortus, whereas the 4 other sheep in this group showed a mean reduction of 99·9% in faecal egg counts and of 97·6% in abomasal worm burden compared to the non-vaccinated controls and the adjuvant controls. The ES-vaccinated sheep showed a 32·2% reduction in parasite egg production and a 63·7% reduction in abomasal worm counts. Analysis of the humoral immune responses revealed no significant differences in antibody recognition of putative protective antigens between the protected and non-protected vaccinated animals. However, a marked lower lymphocyte proliferation response was found in non-protected sheep.