A case-control study using the Veterinary Medical Data Base (VMDB) was conducted to test the hypothesis that increasing height and increasing weight are important risk factors for osteosarcoma in dogs. The role of other host factors was also explored. The cases comprised 3062 purebred dogs with histologically or radiographically confirmed osteosarcoma admitted to 24 veterinary teaching hospitals in the United States and Canada between 1980 and 1994. The controls were 3959 purebred dogs with other diagnoses obtained randomly by frequency matching to cases for institution and year of diagnosis. The risk of osteosarcoma rose with increasing age, increasing body weight, increasing standard weight and increasing standard height. Compared with the German Shepherd breed, the highest risk of osteosarcomas was found for large and giant breeds, while small breeds had reduced risks. A twofold excess risk was observed among neutered dogs. Adjustment of risk estimates for standard height adjusted for standard weight, and vice versa, showed a stronger and more consistent association of osteosarcoma with increasing height than increasing weight.