The causes of sensitive skin, a common problem in patients with acne rosacea or atopic dermatitis, and even in individuals without obvious skin disease, remain unclear. The density of nerve fibers, levels of neuropeptides as well as the nature and number of mast cells may play a role in this connection. Unmyelinated nociceptive neurons mediate most of the sensation from the skin, and a large part of these neurons are characterized by their ability to bind the lectin Banderiaea simlicifolia isolectin IB4 (IB4). We therefore, examined whether the distribution and extent of IB4-labeling is modified in patients with enhanced skin sensitivity compared to controls. We used immunohistochemistry to label IB4-binding elements in skin biopsies from patients with atopic dermatitis. Of the 20 patients with atopic dermatitis subjected to the stinger test, 11 were stinger-positive and 9 stinger-negative. Stinger-positive papillary dermis contained a significantly larger number of IB4 binding cells, which were shown by double staining for tryptase as well to be mast cells. Binding of IB4 was also detected on dermal nerves associated with adnexa structures in the stratium corneum and on keratinocytes.Since IB4 binds to specific carbohydrate moieties, the increased binding of IB4 by mast cells indicates that alterations in their glycoprotein composition may play a pathophysiological role in connection with stinging.