Transforming growth factor-beta (TGF-beta) is known to stimulate dermal wound healing events (fibroplasia and fibrosis). In this study, the effect of TGF-beta on epidermal wound healing (re-epithelialization) was examined. Epidermal cell outgrowth from partial-thickness porcine skin explants was used as an in vitro model for epithelialization. All cultures were grown in medium with 1% fetal bovine serum, which was sufficient for explant viability but low enough to permit measurement of modulation by added factors. Because TGF-beta is known to act in concert with other growth factors, it was evaluated alone and in the presence of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). The results indicate that TGF-beta produced earlier initiation of outgrowth, by 1-2 d compared with control cultures, and increased the rate of outgrowth during the migratory phase of culture (Days 1 -3). Compared to controls, EGF alone produced a greater percentage of growing explants and an increased rate of outgrowth during the mitotic phase (Days 4-7). TGF-beta (1 or 10 mg/ml) and EGF (5 ng/ml) had an additive rather than a synergistic effect on outgrowth. PDGF-treated explants did not show enhanced growth when PDGF (2.5 units/ml) was added alone or together with TGF-beta and EGF. The ability of TGF-beta to produce earlier initiation of outgrowth was not due to an effect on mitosis, because TGF-beta did not increase the incorporation of [³H]thymidine into keratinocytes in the growing epidermal sheets. Rather, it is likely that TGF-beta facilitated keratinocyte migration, possibly by unmasking a receptor on the epidermal cell surface. These results suggest that TGF-beta may play a role in early epidermal wound healing.