Galectin-3, a mammalian galactoside-binding protein, is not expressed in the Jurkat T-lymphoblastoid cell line, However, Jurkat cells express surface glycoprotein receptors for galectin-3, one of which is shown to be the glycosylated heavy chain of CD98 (4F2 antigen), a T-cell activation marker, Addition of galectin-3 to Jurkat cells triggers a sustained influx of extracellular Ca2+ in a concentration dependent manner, The induced increase in cytosolic [Ca2+](i) is blocked by sugar hapten inhibitors of galectin-3. The galectin-3-induced effect is insensitive to voltage-gated Ca2+ channel antagonists such as prenylamine, nifedipine and diltiazem and to pertussis toxin but is inhibited by cholera toxin, The results suggest that galectin-3 released by accessory cells such as macrophages may bind in vivo to T-cell activation antigens and also participate in Ca2+ signalling.