Acquired myasthenia gravis was diagnosed in 6 Newfoundlands from 2 distinct lineages. Three dogs, including 1 pair of littermates, from each lineage were affected. History and clinical signs did not differ from that reported for other dogs with acquired myasthenia gravis. Although a genetic predisposition for development of certain autoimmune diseases in several species has been identified, the immunopathogenesis of myasthenia gravis is multifactorial and includes hormonal, environmental, and infectious disease factors. The high incidence of myasthenia gravis in these 2 distinct lineages of Newfoundlands, a breed with a low relative risk for development of this disease, suggests an underlying genetic mechanism. However, mode of inheritance could not be determined from this small number of dogs. Regardless, breeders should be alerted to this disorder, and they should consider removing Newfoundlands with acquired myasthenia gravis from breeding programs.