N-Propyl-N-nitrosourea (PNU) is a strong carcinogen which induces thymic lymphoma and other tumors in F344 rats. In the present experiment, sequential changes of the thymus, spleen, bone marrow, and other organs were examined histologically in F344 rats which were continuously given PNU in the drinking water. Hematopoietic organs, such as the bone marrow, spleen, and thymus rapidly became hypoplastic. Atrophy of the thymus was followed by repopulation and hyperplasia. The latter was characterized by lymphoblast-like cells and was followed by development of early stage lymphoma, which arose from the 10th experimental week onwards. At first, thymic lymphoma was observed to involve thymic lobes unilaterally, later spreading to bilateral lobes, and at the 16th experimental week, metastatic foci were evident in the bone marrow of one rat. In contrast, hypoplasia of the bone marrow continued until the end of the experiment, while hypoplasia of the red splenic pulp continued until the 12th experimental week. These results indicate that PNU-induced lymphomas arise from within the thymus, although it is not possible to rule out a role for the bone marrow as including target cells of PNU. This PNU-thymic lymphoma system in F344 rats should serve as a good model for the study of experimentally induced thymic lymphoma.