Idiopathic ulcerative dermatitis is a well-recognized disease in C57BL mice and related strains. This disease manifests as a pruritic dermatitis with resulting self-mutilation, dermal ulceration, necrosis, and fibrosis. Ulcerative dermatitis has the ability to confound ongoing research by causing systemic pathologic changes, such as lymphadenopathy and splenomegaly. Although various treatments have been described, none has been curative consistently; therefore, minimizing negative effects on research through prevention of disease is ideal. To identify etiologic factors, we conducted a 2-y retrospective study of 1352 mice with a C57BL/6 genetic background; these mice demonstrated an overall prevalence of 4.1% and a seasonal effect with a peak incidence during midsummer. Corroborating previous studies, our study revealed a disease predilection for female mice. In contrast to prior reports, the disease prevalence was greatest in 10- to 16-mo-old mice. In addition, mice with a C57BL/6 background that were deficient in the gene for inducible nitric oxide synthase had a 50% disease incidence, suggesting a potential animal model for further characterizing the pathogenesis, prevention, and treatment of ulcerative dermatitis.