The catabolic enzyme thymidine phosphorylase (TP) plays a crucial role in nucleic acid metabolism by regulating the availability of thymidine. Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that was recently shown to be TP. The angiogenic properties of PD-ECGF/TP are attributable to a reduction of thymidine levels that results in a promotion of endothelial cell proliferation. Early studies showed a higher concentration of TP in macrophages than in parenchymal cells and in neoplastic than in nonneoplastic tissues. We examined the immunohistochemical expression of PD-ECGF/TP in reactive lymphoid tissues (lymph node and tonsil), as well as in a series of 20 cases of Hodgkin's disease and 31 cases of non-Hodgkin's lymphomas. Macrophages, sinus lining cells, and cells with dendritic morphology, of both follicular dendritic and interdigitating reticular cell type, presented a prominent nuclear and cytoplasmic positivity in reactive lymphoid tissue and in malignant lymphomas. Small lymphocytes and the neoplastic population were always negative, whereas endothelial staining was variable and showed no correlation to the type or grade of the lymphomas. In Hodgkin's disease (with the exception of the nodular lymphocyte predominance type) and some cases of high-grade non-Hodgkin's lymphomas, the positive dendritic cells formed a dense meshwork closely surrounding the neoplastic population. Our results suggest that the reported upregulation of PD-ECGF/TP activity in lymphoid malignancies is attributable to the nonneoplastic population, especially to cells of dendritic morphology.