Hypertrophic Osteodystrophy (HOD) is a common disease of the rapidly growing dogs of the large and giant purebreds. Breeds found to be at higher risk for HOD include the Great Dane, Weimaraner, Irish Setter and German Shepherd Dog. The disease in the Weimaraner is particularly severe, with high mortality rates found in untreated dogs. The age of onset is typically 8 to 16 weeks of age, with males and females equally affected. Recent vaccination with multivalent vaccines (<7 days) is a significant risk factor for occurrence of disease. HOD in the Weimaraner is a genetic disease, with a heritability of 0.35 and an autosomal recessive mode of inheritance. Unfortunately, to date there is no method available to detect carriers other than by test matings and this approach has been ineffective in controlling the disease. DNA samples from 10 separate 3-4 generation families with HOD have been collected, and we propose to identify a marker for susceptibility to HOD in the Weimaraner breeds. Determination of a genetic marker for HOD in the Weimaraner will have immediate impact in the breed for genetic counseling. An understanding of the pathogenesis of HOD and hyper-inflammatory diseases in general may have broad implications for other breeds with these diseases.