A large superficial wound has been experimentally provoked in the cichlid fish Hemichromis bimaculatus to study the interactions between the epidermal cells and the substrate on which they spread, on the one hand, and the restoration of the subepidermal tissues and the epithelial-mesenchymal interactions preceding scale regeneration, on the other hand. The re-epithelialization process, e.g., migration, spreading, differentiation, and proliferation of the epidermal cells, has been followed step by step, using light, scanning and transmission electron microscopy, and tritiated thymidine incorporation, until complete reorganization of the healing epidermis. Wound healing is fast (500 microm/hr) and proceeds centripetally from the wound margins. The epidermal cells spread on a wound surface which is composed of two different matrices: the remains of basement membrane materials covering the scale-pockets, and collagen fibrils of cut dermal strips. Even though both matrices favour cell spreading and attachment, migrating cells show a different behaviour. The re-epithelialization of the wound follows an orderly sequence similar to amphibian and mammalian wound healing, i.e., a "leap frog" mechanism of cell locomotion involving three epidermal layers. The basal layer cells, which spread on the substrate, and the superficial layer cells which protect the epidermis, differentiate first. Whatever the type of substrate over which the epithelium spreads (basement membrane material or collagen fibrils), the epidermal basal layer cells differentiate as soon as they become attached. The incorporation of tritiated thymidine has revealed that there is no proliferation in the healing epidermis until after complete closure of the wound, but that the rapid re-epithelialization of the large surface requires the recruitment of epidermal cells at the wound margins. The present study offers new data on the dynamics of re-epithelialisation and on the resistance of cichlid skin to such wounds. It is also clearly shown that the epidermal basal layer cells differentiate rapidly, a step which is interpreted as the first stage of epithelial-mesenchymal interactions that will lead to scale regeneration.