The process by which wounds reepithelialize remains controversial. Two models have been proposed to describe reepithelialization: the "sliding" model and the "rolling" model. In the "sliding" model, basal keratinocytes are the principal cells responsible for migration and wound closure. In this model, basal and suprabasal keratinocytes remain strongly attached to leading edge basal keratinocytes and are then passively dragged along as a sheet. The "rolling" model postulates that basal keratinocytes remain strongly attached to the basement membrane zone while suprabasal keratinocytes at the wound margin are activated to roll into the wound site. The purpose of this study was to determine which populations of keratinocytes are actively involved in reepithelialization. We evaluated expression of keratins K14, K15, K10, K2e, and K16 as well as the proliferation marker Ki67 in the migrating tongue of normal human incisional 1-hour to 28-day wounds and normal human 3 mm diameter excisional 1- to 7-day wounds. Our results show dramatic changes in phenotype and protein expression of keratins K10, K2e, K14, K15, and K16 in suprabasal keratinocytes in response to injury. We conclude that this large population of suprabasal keratinocytes actively participates in wound closure.