We identified the C‐type‐lectin‐like receptor, Dectin‐1, as the major receptor for fungal β‐glucans on murine macrophages and have demonstrated that it plays a significant role in the cellular response to these carbohydrates. Using two novel, isoform‐specific mAb, we show here that human Dectin‐1, the β‐glucan receptor (βGR), is widely expressed and present on all monocyte populations as well as macrophages, DC, neutrophils and eosinophils. This receptor is also expressed on B cells and a subpopulation of T cells, demonstrating that human Dectin‐1 is not myeloid restricted. Both major functional βGR isoforms – βGR‐A and βGR‐B – were expressed by these cell populations in peripheral blood; however, only βGR‐B was significantly expressed on mature monocyte‐derived macrophages and immature DC, suggesting cell‐specific control of isoform expression. Inflammatory cells, recruited in vivo using a new skin‐window technique, demonstrated that Dectin‐1 expression was not significantly modulated on macrophages during inflammation, but is decreased on recruited granulocytes. Despite previous reports detailing the involvement of other β‐glucan receptors on mature human macrophages, we have demonstrated that Dectin‐1 acted as the major β‐glucan receptor on these cells and contributed to the inflammatory response to these carbohydrates.