The failure of chronic wounds to heal remains a major medical problem. Recent studies have suggested an important role for growth factors in promoting wound healing. We investigated the mitogenic effect of basic fibroblast growth factor (FGF), insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF), comparing their effects with those of media alone (MEM) in a human skin explant model. A stable organ culture system for maintaining the histologic structure of human epidermis for 10 days in vitro was developed. DNA synthesis was measured on Days 1, 3, and 7 of organ culture using [3H]thymidine ([3H]thy) uptake and expressed as cpm/mg dry weight (mean +/- SEM). FGF, IGF-1, and EGF were each capable of stimulating [3H]thy uptake on Day 1 of culture (2372 +/- 335 FGF, 2226 +/- 193 IGF-1, 4037 +/- 679 EGF vs 1108 +/- 70 MEM, P < 0.05). IGF-1 and EGF also stimulated [3H]thy uptake on Days 3 and 7 of culture. The organ culture system was further employed to observe epidermal outgrowth. Longest keratinocyte outgrowth from the explant periphery (simulating epithelial regeneration from the wound edge) was observed on Day 7. EGF resulted in maximum stimulation of epithelial outgrowth (440 +/- 80 microns), followed by FGF (330 +/- 56 microns), IGF-1 (294 +/- 48 microns), and MEM (189 +/- 50 microns). We postulate, therefore, that FGF, IGF-1, and EGF are important mitogens for wound healing and that EGF in particular is capable of stimulating epithelialization.(ABSTRACT TRUNCATED AT 250 WORDS)