beta-Glucans are well known leukocyte activators that have shown protective benefits in a variety of animal disease models, yet the mechanism of action of these carbohydrates remains unknown. We have shown that Dectin-1, a murine type II C-type lectin-like receptor, was able to non-opsonically recognize beta-1,3 and beta-1,6 linked glucan rich particles and intact yeast. Dectin-1 is widely expressed in murine tissues, particularly on the monocyte/macrophage and neutrophil lineages, on dendritic cells (DC) and at a lower level on a sub-population of T cells. The human homologue of Dectin-1 was identified and is functionally similar to the murine molecule. Human Dectin-1 differs from the murine molecule in that it is expressed as two major splice variants that are selectively expressed in particular leukocyte populations. In addition to beta-glucans, Dectin-1 also recognizes an endogenous ligand on T cells. The ligand and the immunological role of Dectin-1 mediated T cell interactions remain to be described.