Serum lactate dehydrogenase (LDH) activity is increased in many tumor-bearing patients and can be used as a prognostic marker. We studied serum LDH concentration in 94 consecutive patients with non-Hodgkin’s lymphoma who where histologically classified according to the Kiel Classification and were grouped according to the Non-Hodgkin’s Lymphoma Pathologic Classification Project Working Formulation. 74 patients were studied at diagnosis, and 20 of them (27%) had an LDH level higher than 250 U/l. High LDH levels were more frequent in cases of true histiocytic, high-grade, and intermediate-grade malignancy lymphoma (4 of 7, 7 of 14, and 7 of 20, respectively) than in cases of low-grade lymphoma (2 of 33). A close relationship of LDH to several prognosis-related disease features was found, including general symptoms, bulky disease, big mediastinal tumor, huge hepatosplenomegaly, bone marrow involvement, and a leukemic syndrome. LDH was higher than normal in a high proportion of cases who were studied in relapse (13 of 20, 65%). These data suggest that in non-Hodgkin’s lymphomas the LDH serum concentration is not independent of other disease features, so that the prognostic value of LDH is probably lower than expected from previous studies. Serum LDH activity decreased to normal in all cases of complete remission, but also in cases of partial remission, suggesting that measuring enzyme activity is of a limited usefulness for detecting and monitoring minimal residual disease. For that purpose, LDH isoenzyme studies would be more appropriate.