Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that modulates cell proliferation and differentiation in many cell types and accelerates tissue repair response. In this study, expression of TGF-beta was investigated immunohistochemically in the healing of central 3 mm epithelial wounds of vitamin A-deficient (A-) rat and pair-fed controls. In control rat corneas, a positive reaction to TGF-beta was not evident during wound healing. In A- rat corneas at 4 hr post-abrasion, acute inflammatory cells showing high positivity to TGF-beta appeared in the peripheral stroma and gradually spread to the central cornea. By 24 hr, these cells accumulated and formed a pseudomembrane in the epithelial defect, which also showed an intense positivity to TGF-beta, suggesting that the peptide participates even in the acute inflammatory response. From about 16 hr post-injury, many fibroblasts revealing intense positivity to TGF-beta infiltrated the entire stroma and were part of the healing process. Reepithelialization occurred over the pseudomembrane and was completed by 48 hr. The central cornea showed remodeling of collagen structure and neovascularization. Fibroblasts containing TGF-beta were seen in the stroma, indicating that TGF-beta plays an important role in corneal wound healing. Indeed, in the absence of vitamin A, a common modulator of cell differentiation, TGF-beta may play a more important role in wound healing than in the normal state.