To evaluate epidermal-dermal interdependency during the wound-healing process, the proline analogue L-azetidine-2-carboxylic acid (LACA) was topically applied to split-thickness skin wounds in young domestic pigs. LACA is incorporated into collagen and the collagen containing this analogue is extruded from the cell at a decreased rate. Wounds were assigned to one of three treatment groups: control (no treatment), LACA (0.2 mg in 0.1ml of water), and placebo (0.1 ml of water). On days 2 through 10 after wounding, several wounds from each treatment group were excised and the epidermis was separated from the dermis. The epidermal sheet containing the wound was evaluated for integrity and the underlying dermis was assayed for hydroxyproline. LACA was found to decrease both the rate of reepithelialization and the hydroxyproline levels. LACA did not seem to directly affect the epidermis, since epidermal collagen did not differ markedly. These results suggest that during wound healing, the migrating epithelium is partially dependent on the underlying connective tissue.