Alkaline phosphatase (ALP) activity was evaluated histochemically and cytochemically in concert with immunologic technics in 60 cases of non-Hodgkin's lymphomas and lymphocytic leukemias. Surface membranes of neoplastic cells were positive for ALP only in certain B-cell malignancies: 3 of 6 lymphocytic lymphomas of intermediate differentiation, 4 of 13 nodular lymphomas, and 1 of 7 Burkett's lymphomas. All other B-cell tumors, including chronic lymphocytic leukemia, well-differentiated lymphocytic lymphoma, and diffuse "histiocytic" lymphoma, were ALP-negative. The neoplastic cells of Sezary syndrome and lymphoblastic lymphoma were also consistently negative for ALP. In control lymph nodes ALP-positive lymphocytes were present only in primary follicles and in mantle zones of secondary follicles. ALP-positive lymphomas appear to be neoplastic counterparts of these normal lymphocytes, not only cytochemically, but also with respect to their morphologic and immunologic characteristics. Furthermore, histochemical inhibition tests suggested that the ALP activity demonstrated may reflect a newly recognized, unique isoenzyme.