CD30 is a surface marker for neoplastic cells of Hodgkin’s lymphoma and shows sequence homology to members of the tumor necrosis factor (TNF) receptor superfamily. Using a chimeric probe consisting of the extracellular domain of CD30 fused to truncated immunoglobulin heavy chains, we expression cloned the cDNA cognate from the murine T cell clone 789. The encoded protein is a 239 amino acid type II membrane protein whose C-terminal domain shows significant homology to TNFa, TNFf3, and the CD40L. Crosshybridization to an induced peripheral blood T cell cDNA library yielded the human homolog, which is 72% identical at the amino acid level. The recombinant human ligand enhances the proliferation of CD3-‘activated T cells yet induces differential responses, including cell death, in several CD30+ lymphomaderived clones. The human and murine genes map to 9933 and the proximal region of chromosome 4, respectively.