In total, 19 8-month-old Texel sheep were used to study the isotype-specific serum antibody responses against infective larvae and adult worms of Haemonchus contortus. Group Group 1 sheep (n = 7) were infected with 20,000 L3 larvae (Week 0), treated with ivermectin 6 weeks post-infection and subsequently challenged at Week 10 of the experiment. This challenge consisted of a trickle infection of 10,000 L3 larvae per week for 5 weeks. Group 2 sheep (n = 7) received a single infection at Week 10 of the experiment, and Group 3 (n = 5) served as a non-infected control group throughout the entire experiment. Individual blood and faeces samples were collected at weekly intervals. The immune responses were monitored by ELISA and Western blotting. The secondary immune response coincided with a significant reduction of the Haemonchus egg output and reduction of worm counts. Both primary and challenge infections induced humoral immune responses, and ELISA revealed that the most dominant serum antibody responses belong to the IgG1 isotype and to a lesser extent to IgG2. IgM and IgA responses were less dominant. Western blotting experiments demonstrated that many antigens were commonly recognized by antibodies from both primary and challenge infected animals. However, sera of immune animals specifically reacted with low molecular weight proteins. In particular, a 24 kDa antigen present in adult worms appeared to be specifically recognized.