The pretreatment serum lactate dehydrogenase level (LDH) was the single most important prognostic variable in 30 patients with diffuse histiocytic lymphoma treated between January 1973 and January 1977 with a poly-drug chemotherapy program called the cyclophosphamide L2 protocol at the Memorial Sloan-Kettering Cancer Center. A highly significant difference was found between the survival patterns of patients with LDH levels of 500 U or less and those with LDH levels greater than 500 U. (Two-year survival rates were 67% and 13%, respectively.) A similar trend was observed for 25 patients with diffuse, poorly differentiated lymphocytic lymphoma treated with the same protocol, although this difference was not statistically significant. (Corresponding two-year survival rates were 74% and 33%, respectively.) The association of LDH level with survival was evident even after adjustment for other factors of potential prognostic significance. Pretreatment serum LDH determinations may provide a useful means of stratifying patient populations when comparing treatment programs for advanced stage non-Hodgkin's lymphoma.