In two blood cell types, peritoneal murine macrophages and Jurkat cells (a human T cell line), we have examined whether a Na+/Ca2+ exchange was present and what could be its functional importance. In non-stimulated macrophages, the intracellular Ca2+ concentration, [Ca2+]i, was unchanged when Li+ was substituted for external Na+. However, after stimulation by platelet-activating factor (PAF), the Ca2+ response was larger when the extracellular solution contained Li+ rather than Na+ ions. In stimulated macrophages, the rate of Ca2+ extrusion was smaller in a Li(+)- than in a Na(+)-containing medium. The net electrochemical gradient for ionic movements through the Na+/Ca2+ exchanger, during the course of the response of macrophages to PAF, was determined by combining the measurements of membrane potential (in patch-clamp), of [Ca2+]i (with fura-2), and of the intracellular Na+ concentration (with sodium-binding benzofuran isophthalate). These results show that macrophages possess a Na+/Ca2+ exchange that only functions as a Ca2+ extruder, and this only when [Ca2+]i has been increased, for instance following PAF stimulation. In T lymphocytes, before or after stimulation by an anti-CD3 antibody, no Na+/Ca2+ activity could be detected by measuring either [Ca2+]i, or the rate of Ca2+ extrusion. Even if a Na+/Ca2+ exchanger was present in these cells, its equilibrium potential would be such that it would not allow Ca2+ influx but only Ca2+ extrusion.