An unusual isozyme of lactate dehydrogenase, lactate dehydrogenase associated with Kirsten murine sarcoma virus (LDHk) was found in the sera of many patients with malignant tumors, while the sera of healthy persons had little or no such activity. This isozyme was detectable only when assayed in a nitrogen atmosphere, and its activity showed little or no relationship to the total lactate dehydrogenase activity as measured by a standard clinical assay. The activity of serum LDHk appeared to be correlated with the presence of known metastases. Increased serum LDHk appeared in a wide variety of patients with cancer, although it appeared to be more common in certain types of cancer. Increased serum LDHk activity was also found in the sera of some patients with nonmalignant disease. The activity of serum LDHk may be useful to monitor recurrence or response to therapy in certain types of cancer.