The effect of topical application of epidermal growth factor (EGF) and platelet-derived growth factors (PDGFs) on the levels of EGF-R and PDGF-R proteins and their tyrosine phosphorylation were analyzed during an acute cutaneous wound healing process in mice. The growth factor-treated wounds had optimum levels of receptor proteins as early as day 1 compared with the control, which had only a basal level. Analysis of the tyrosine phosphorylation of the receptor proteins in control and growth factor-treated wounds indicated that they were phosphorylated until day 5 after wounding. Only the mature forms of alpha-PDGF-R and beta-PDGF-R proteins were phosphorylated and not their precursors. Our results show that rapid attainment of maximum levels of growth factor receptor proteins and their tyrosine phosphorylation as early as day 1 and the maintenance of the same until day 3 appear to aid faster and better wound healing. Topical application of PDGF-AA alone did not facilitate the wound healing process and it also antagonized the EGF-medicated wound healing when applied premixed with EGF or within 30 minutes after EGF application. Under these conditions, the receptor proteins were not phosphorylated. Thus, an increased and sustained level of EGF-R and PDGF-R proteins and their tyrosine phosphorylation appear to accelerate the wound healing process.