Adult wounds heal with scar formation, whereas fetal wounds heal without scarring and with a lesser inflammatory and cytokine response. We reasoned that a strategy employing antisense oligodeoxynucleotides (ODN) complementary to transforming growth factor (TGF)-beta-1 mRNA might decrease the scarring of dermal wounds in the mouse. To evaluate this concept, we tested the effects of antisense ODN targeted to TGF-beta 1 mRNA by topical application of the ODN on the skin wound. Phosphorothioation of ODN to retard their degradation. When antisense TGF-beta 1 ODN were applied on the wound site, there was marked reduction of scarring compared with a control wound site. This effect of antisense TGF-beta 1 ODN on scar formation was associated with decreased expression of the TGF-B1 gene. However, sense TGF-beta 1 ODN had no effect on the expression of the TGF-beta 1 gene. In addition, control wounds healed with excessive fibrosis compared with the antisense-treated wounds. In conclusion, our results indicate that antisense TGF-beta 1 ODN could be used for ameliorating scar formation during wound healing.