Seventy-three percent of chickens inoculated with the chick syncytial strain of reticuloendotheliosis virus (REV) at hatching developed lymphomas by 39 weeks of age. Neonatal treatment with cyclophosphamide or surgical bursectomy at 2, 4, 8, or 12 weeks of age significantly (P less than 0.01) reduced lymphoma development. In a further experiment, surgical bursectomy of REV-infected chickens followed by intravenous inoculation of the chickens with a single cell suspension of their own bursa cells at 2, 4, 9, or 13 weeks of age resulted in lymphoid tumors in chickens treated at 9 or 13 weeks but not in chickens treated at 2 or 4 weeks of age. Furthermore, this treatment did not shorten the incubation period for lymphoma development. These findings argue very strongly that transforming target cells are primarily in the bursa of Fabricius. The data also suggest that a minimum residency of 4 weeks in the bursa is required for infected bursa cells to become transformed. Therefore, lymphomagenesis induced by REV in chickens appears similar to that induced by the avian leukosis virus group.