The article introduces BID, a novel protein with only the BH3 domain that interacts with both death agonists (e.g., BAX) and antagonists (e.g., BCL-2) of the BCL-2 family. BID lacks a carboxy-terminal signal-anchor segment and is found in both cytosolic and membrane locations. It counteracts the protective effect of BCL-2 and induces apoptosis by activating ICE-like proteases. Mutagenesis studies reveal that an intact BH3 domain is essential for BID's interaction with BCL-2 or BAX and its death-promoting activity. The data suggest that BID serves as a death ligand for the membrane-bound receptor BAX, supporting a model where BID represents a death ligand for BAX.The article introduces BID, a novel protein with only the BH3 domain that interacts with both death agonists (e.g., BAX) and antagonists (e.g., BCL-2) of the BCL-2 family. BID lacks a carboxy-terminal signal-anchor segment and is found in both cytosolic and membrane locations. It counteracts the protective effect of BCL-2 and induces apoptosis by activating ICE-like proteases. Mutagenesis studies reveal that an intact BH3 domain is essential for BID's interaction with BCL-2 or BAX and its death-promoting activity. The data suggest that BID serves as a death ligand for the membrane-bound receptor BAX, supporting a model where BID represents a death ligand for BAX.