We evaluated the effect of topical epidermal growth factor treatment on healing of chronic wounds in a prospective, open-label, crossover trial. Five males and four females who ranged in age from 40 to 72 years (average 57 +/- 9 years) were enrolled. Four patients had adult-onset diabetes mellitus, two had rheumatoid arthritis, two had old burn scars, and one had a failed abdominal incision. The average duration of the ulcers prior to treatment with epidermal growth factor was 12 +/- 5 months (range 1 to 48 months). Following failure of the wounds to heal with conventional therapies, including debridement, skin graphs, and vascular reconstruction, wounds were treated twice daily with Silvadene alone for periods ranging from 3 weeks to 6 months. No evidence of healing was observed in any of the patients' wounds during Silvadene treatment, and patients were crossed over to twice a day treatment with Silvadene containing 10 micrograms epidermal growth factor per gram. Wounds of eight patients healed completely with epidermal growth factor-Silvadene treatment in an average of 34 +/- 26 days (mean +/- SD, range 12 to 92 days) and did not reoccur for periods ranging from 1 to 4 years. One patient failed therapy. These results suggest that topical treatment of chronic wounds with epidermal growth factor may stimulate healing.