We investigated the mRNA content for tumor necrosis factor (TNF)/cachectin and lymphotoxin (LT) in tumoral tissues of a prospective series of 35 non-Hodgkin's (NHL) and 23 Hodgkin's (HL) lymphomas, to assess their postulated contribution to systemic symptoms. Total RNAs were extracted from diagnostic tissue specimens and submitted to Northern blot analysis, using specific TNF and LT cRNA probes. High amounts of TNF mRNA were found exclusively in NHL (12/35). The majority (9/12) of these were low grade B-cell NHL, which contained a uniform population of malignant cells. In contrast, abundant LT mRNA production was detected in most HL (21/23) and in 19 of 35 NHL. The highest LT mRNA levels were observed in high grade NHL and in lymphocytic predominant subtypes of HL specimens. A significant correlation was found between TNF/cachectin and LT gene expression in NHL and the presence of constitutional symptoms. The biologic and prognostic implications of these preliminary findings are presently unknown, but they demonstrate that lymphoma tissues sharing common histologic features are highly heterogeneous in their ability to synthesize cytokines susceptible to playing a role in the growth control of malignant cells. These results suggest that the evaluation of TNF/cachectin and LT production in lymphomas may help to elucidate the mechanisms of tumoral fever and cachexia.