The P-2Z receptor is responsible for adenosine triphosphate (ATP)-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Other ATP-gated channels, the P-2X receptors, are permeable only to small cations. Here, an ATP receptor, the P2X(7) receptor, was cloned from rat brain and exhibited both these properties. This protein is homologous to other P-2X receptors but has a unique carboxyl-terminal domain that was required for the lytic actions of ATP. Thus, the P2X(7) (or P-2Z) receptor is a bifunctional molecule that could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells.