The dynamics of the anti-Hypoderma antibody response after a treatment with injectable and pour-on ivermectin against first instars of Hypoderma sp. were determined in naturally infested cows. Cattle were randomly assigned to three groups: group 1, which served as an untreated control; group 2, treated with pour-on ivermectin at a dose of 500 μg/kg of body weight, and group 3, which received 200 μg/kg of body weight of ivermectin by subcutaneous injection. Both ivermectins showed total efficacy against L-1 of Hypoderma sp. In untreated control animals, grubs became detectable in the 2 mo after treatment. Indirect enzyme-linked immunosorbent assay (ELISA) showed a significant increase in group 3 antibody levels 1 mo after treatment, whereas in group 2 the increase was not significant. Following the peak of antibody activity in group 3, antibody levels declined at a faster rate than in those treated topically. In both treated groups, cattle remained serologically positive for 4 mo after ivermectin treatment. Thus, serological surveillance programs for cattle grubs conducted during this posttreatment period will not be influenced by treatment with ivermectin. The persistence of antibody levels after larval destruction makes the indirect ELISA unsuitable for the prediction of the efficacy of treatment.