The histologic organization of lymphoid and nonlymphoid (epithelial and interdigitating) cells in a thymoma has been compared to that of the normal thymus. Enzyme and immunohistochemical methods were applied, using both conventional antisera (to cytokeratin) and monoclonal antibodies (to epithelial cells, HLA-DR and lymphoid subsets). Throughout the tumor, the epithelial cells shared phenotypical similarities with the epithelial cells of thymic medulla (RFD-4 positive, cytokeratin strongly positive, and HLA-DR essentially negative). On the other hand, the lymphoid cells were heterogeneous in phenotype and distribution, and "mimicked" the distribution seen in the normal infant thymus. Immature thymocytes of cortical type (TdT+, OKT6+, OKT3-) were predominant in the areas with moderate lymphocytic infiltration (ML). Mature T-lymphocytes (TdT-, OKT6-, OKT3+) were found mainly in areas with scanty lymphocytes (SL) together with an additional population of HLA-DR positive interdigitating and HLA-DR+, OKT6+ Langerhans'-type cells. These findings indicate that in thymoma tissue, the lymphoid elements of cortical type are apparently surrounded by an inappropriate (medullary) epithelium.