The lymphokine tumor necrosis factor (TNF) has a well-defined role as an inducer of inflammatory responses; however, the function of the structurally related molecule lymphotoxin (LTalpha) is unknown. LTalpha is present on the surface of activated T, B, and LAK cells as a complex with a 33 kd glycoprotein, and cloning of the cDNA encoding the associated protein, called lymphotoxin beta (LTbeta), revealed it to be a type II membrane protein with significant homology to TNF, LTalpha, and the ligand for the CD40 receptor. The gene for LTbeta was found next to the TNF-LT locus in the major histocompatibility complex (MHC), a region of the MHC with possible linkage to autoimmune disease. These observations raise the possibility that a surface LTalpha-LTbeta complex may have a specific role in immune regulation distinct from the functions ascribed to TNF.