BACKGROUND: The prevalence of pressure ulcers of the foot is a major health care problem in frail elderly patients. A pressure sore dramatically increases the cost of medical and nursing care, and effective treatment has always been an essential nursing concern. Management options for pressure ulcers include local wound care; surgical repair; and, more recently, topical application of growth factors. OBJECTIVE: To examine the effects of topical treatment with nerve growth factor in patients with severe, noninfected pressure ulcers of the foot. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Teaching nursing home of Catholic University of the Sacred Heart, Italy. PATIENTS: 36 persons with pressure ulcers of the foot. INTERVENTION: 18 patients received nerve growth factor treatment, and 18 patients received only conventional topical treatment. MEASUREMENTS: The course of the ulcers during follow-up was evaluated by tracing the perimeter of the wound onto sterile, transparent block paper and determining the stage. RESULTS: At baseline, the treatment and control groups did not differ across demographic variables, clinical characteristics, and functional measures. The mean area (+/-SD) of the ulcers was 1012 +/- 633 mm2 in the treatment group and 1012 +/- 655 mm2 in the control group (P > 0.2). The average reduction in pressure ulcer area at 6 weeks was statistically significantly greater in the treatment group than in the control group (738 +/- 393 mm2 vs. 485 +/- 384 mm2; P = 0.034). CONCLUSION: Topical application of nerve growth factor may be an effective therapy for patients with severe pressure ulcers.