Activated T cells express a number of cell surface proteins that play an important role in cell contact-dependent interactions with cells in the immune system, including B cells, macrophages and other T cells. Among these T cell-expressed proteins are members of the TNF ligand family, which includes TNF, lymphotoxin (LT)-alpha and -beta, and the ligands for CD27, CD30, CD40, 4-1BB, OX-40, and Fas. The recent cloning of a number of these ligands has paved the way for a detailed analysis of the role of these molecules in immune responses. Initial studies have suggested that most, if not all, of these ligands co-stimulate T-cell proliferation. It is becoming increasingly apparent, however, that members of the TNF ligand family play unique and critical roles in both the development of the immune system and in immune responses to specific pathogens.