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AKR mice spontaneously develop T-cell leukemias in the thymus late in the first year of life. These neoplasms arise following the appearance in the thymus of a recombinant retrovirus but can be prevented by thymectomy, indicating a role for both virus and elements of the thymic microenvironment in leukemogenesis. The intrathymic appearance of recombinant retrovirus was examined at ages leading up to leukemogenesis in order to identify and characterize the microenvironments in which the virus is first expressed. A stromal cell, the macrophage, was found to be the first thymic element to produce detectable levels of recombinant retrovirus, approximately 12 weeks before thymocytes. This observation provides a mechanism to reconcile viral leukemogenesis with the requirement for an intact thymus. Thus, a nonlymphoid cell, the macrophage, may play a critical role in the development of lymphoid neoplasia.