The integrin receptor family plays a fundamental role in mediating cell attachment to a variety of extracellular matrix molecules. In normal human epidermis, the α2β1, α3β1,α6β4 and αvβ5 integrin heterodimers are expressed and appear largely confined to the basal cell layer. In the present study, β1,β4, and αv integrin expression in the epidermis during wound healing in humans was examined. Punch biopsies were performed on healthy volunteers. At daily intervals up to day 8, and at days 11, 14, 21, and 28, the wound site was surgically removed. Using immunofluorescence microscopy, several modifications of the integrin expression pattern were observed on migrating keratinocytes during the re-epithelialization phase of the wound-healing process: i) αv expression was strongly enhanced and polarized at the basal pole of basal keratinocytes; ii) among the β1 integrins, α3β1 was overexpressed and distributed over the entire basal keratinocyte membrane and a weak &α5β1 reactivity became evident; and iii) α6β4 was detected as a linear staining along the newly forming dermal-epidermal junction. Moreover, both during the re-epithelialization phase and during the first 2 weeks after wound closure, α3, α6,αv,β1, and β4 were no longer confined to the basal layer, as in normal epidermis, but were also found on several suprabasal cell layers. These results suggest that α_vβ₅, α₃β₁, and α₅β₁ may be the main integrin receptors mediating keratinocyte spreading and migration over the provisional matrix of the wound bed.