Immunomodulation by Ostertagia ostertagi and the effects of strategic anthelmintic treatments were studied in 3 groups of 6 calves each: an infected group, inoculated with 100,000 third-stage larvae (L3)/calf at 1 and 28 days; an infected-treated group, similarly inoculated, but treated with ivermectin 9 days after each inoculation; and a noninfected control group. Calves were grazed on 2 previously clean pastures, with the infected and infected-treated calves sharing 1 pasture. All calves were inoculated at 12 weeks with Brucella abortus and infectious bovine rhinotracheitis vaccines, and at 13 weeks with a soluble O ostertagi L3 extract (SLE). Infected and infected-treated calves had lower blood lymphocyte responses to phytohemagglutinin than did control calves at 2, 4, and 14 weeks, whereas the infected calves had higher responses at 6 and 8 weeks (P < 0.05). Responses to pokeweed mitogen followed a similar pattern, whereas those to SLE were low in all calves. Infected and infected-treated calves had increased values of IgG1 to excretory-secretory antigens of L4 larvae, but no changes in the values of IgG1 to SLE. They also had lower values of IgG and IgM to B abortus and antibodies to infectious bovine rhinotracheitis at 13 weeks. The infected-treated calves, however, had higher blood lymphocyte and monocyte counts and lower eosinophil count than did infected calves. They also had reduced abomasal mucosa thickness, abomasal wall weight, and abomasal lymph node weight than infected calves. It was concluded that O ostertagi causes nonspecific suppression of cellular and humoral immunity, hypersensitivity reactions coexisted with immunosuppression, and strategic anthelmintic treatments attenuated hypersensitivity reactions and initiated better immune responses.