Cystic fibrosis (CF) is a common autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CF affects multiple organs, including lungs, pancreas, intestine, liver, sweat glands, gallbladder, and the male genital tract. Airway infection and inflammation currently cause most of the morbidity and mortality. Although several therapies have improved the lives of patients, current treatments are inadequate and CF remains a lethal disease. Our knowledge about the pathogenesis of the disease, its progression, and the state of the neonatal lung is inadequate. These gaps in our knowledge have hindered attempts to develop better treatments and preventions for CF lung disease. A major impediment to addressing these issues had been limitations of animal models. Although mouse strains carrying null and missense CFTR mutations have made enormous contributions, CF mice do not develop the airway or pancreatic disease typically found in humans. We have generated CF ferrets and pigs that replicate many of the key features of human CF disease including intestinal obstruction, exocrine pancreatic destruction, micro-gallbladder, vas deferens abnormalities, focal biliary cirrhosis, congenital airway structural abnormalities, and airway and sinus infection with time. The goals of the Animal Models Core will be: (1) To provide Program investigators with non-CF and CF ferrets and pigs so that they can successfully complete their project aims. (2) To build new genetically engineered CF ferret models that express CFTR in a regulated fashion. (3) To assist projects in carrying out small molecule delivery, the harvesting of biologic samples from live animals (e.g., bronchoalveolar lavage fluid, blood, and microbiological samples), and the care and analysis of study animals. (4) To assist projects in record keeping and coordinate animal usage among projects. The Animal Models Core will function seamlessly through already established interactions with the Project Leaders, Pathology Core, In Vitro Models and Cell Culture Core, and the Administrative Core. The success of the Animal Models Core is ensured because of the commitment, experience, and expertise that the personnel bring to the Core.