Many immune and inflammatory cells express a plasma membrane receptor for extracellular ATP, termed the P2Z purinoceptor, which appears to be coupled to a plasma membrane pore. The physiological role of such a molecule is generally unknown, except for the striking susceptibility to ATP-mediated cytotoxicity that it confers. The receptor is upregulated in human monocytes by interferon gamma and is also expressed during macrophage differentiation. Here, Francesco Di Virgilio discusses recent information on this receptor, and suggests a possible role for it in the immune and inflammatory response.