The incidence and case distribution of lymphosarcoma were determined prospectively in one breed of dogs, the bull mastiff. Fifty-nine dogs from three households were followed for 3 years. Two of the households had a previous history of lymphosarcoma cases, whereas the third had no history of such cases. During the survey period, 9 of the 59 dogs died from lymphosarcoma with multiple cases occurring in each household. On the basis of this survey, the annual incidence rate in the general bull mastiff population is likely to be on the order of 5,000 cases per 100,000 dogs, which constitutes the highest incidence rate recorded in this species. The distribution of the cases displayed a familial pattern. The possible involvement of genetic and infectious factors in the development of this disease pattern is discussed.