The purpose of our study was to identify evidence for genetic control of immune responses in cattle. To address this question, we evaluated the variation of antibody responses induced by vaccination with Brucella abortus Strain 19, a live attenuated bacterial vaccine, in large half-sibling families. The data were analyzed using a parametric statistical model that incorporated the effects of sire, bovine major histocompatibility complex (BoLA) types and parameters related to the experimental design. The BoLA types represented a readily identifiable marker, analogous to those known to be associated with genetic control of immune responses in other mammals. Variation between individual animals within our test population was significant but we were able to identify both individual animals and families with high or low antibody production phenotypes. In several cases, these traits were significantly correlated with individual bulls, suggesting the existence of sire effects, or with individual BoLA types. These findings are consistent with the theory that at least two separate genes or genetic systems contribute to the control of bovine antibody responses to B. abortus vaccination. These genetic effects are likely to be analogous to those identified in several species of laboratory rodents and humans.