(C57BL/6 X DBA/2) F1 hybrid mice injected at the age of 6 weeks with C57BL/6 spleen cells were killed at regular intervals from 1 week to 15 months after the administration of parental cells and their tissues were examined histologically. The earliest changes in the spleen and lymph nodes consisted of proliferation of large mono-nuclear cells, together with varying degrees of small lymphocyte depletion. Thereafter, three types of abnormalities of the lymphoid tissue were found: (1) atrophy, (2) expansion of lymph follicles into irregular masses of pleomorphic cells, (3) replacement of lymph follicles by histiocytes. The latter two lesions are thought to represent the antecedents of the malignant lymphomas which may develop in the long-term survivors of the graft-versus-host reaction. These findings support the concept that the transition from an immunological disorder, allogeneic disease, to a malignant growth is part of a continuous process initiated by the transplantation of foreign lymphoid cells. Thymic atrophy was not a feature in the present parent-hybrid combination, suggesting that the manifestations of the graft-versus-host reaction are not necessarily dependent on thymic destruction.