The success of strategies that therapeutically exploit immune responses to self antigens such as those expressed on melanoma cells to treat patients suffering from melanoma is well established. In transgenic Alzheimer's disease (AD) animal models, elimination of β-amyloid (Aβ) pathology using Aβ immunization galvanized the AD research community a decade ago. Using an animal model of AD with closer parallels to human AD, the cholesterolemic rabbit model, we tested immunotherapeutic strategies that could maximize humoral immune responses while minimizing proinflammatory responses. The finding that some patients with AD enrolled in a clinical trial to inoculate against A experienced a misdirected polarization of Th cells reminds us that our knowledge of T cell biology, immune regulation, and the precise functional properties of adjuvants is incomplete. In this article, we review this knowledge and consider the advantages of the rabbit for immunological studies. The langomorph species is proximate to primates on the phylogenetic scale, its amino acid sequence of A is identical to the human A sequence, and the rabbit model system is extensively characterized on a form of associative learning with parallels in normal aging in rabbits and humans that is severely impaired in human AD. Cholesterol-fed rabbits treated with Aβ immunotherapy generate high titer anti-Aβ responses. The cholesterol-fed rabbit model of AD with its close parallels to human genetics and physiology, along with its validity from molecular to cognitive levels as a model of human AD, provides a promising vehicle for development of immunotherapies.