This double blind controlled study examined whether oxygen-derived free radicals interfere with the healing of venous ulceration occurring on the medial side of the leg for the first time. Graduated compression bandages exerting a mean ankle pressure of 42.1±0.3 mmHg and a mean pressure of 17.3±0.2 mmHg just below the knee healed 70% of ulcers within 12 weeks (n=44). Addition of the radical scavengers allopurinol (n=45) or dimethyl sulfoxide (n=44) to the compression bandages (daily application of the powder for 7 days, then once weekly applications to the end of the study at 3 months) significantly (p < 0.01) stimulated the healing of venous ulceration relative to controls when studied 4, 8, and 12 weeks after commencing treatment. After 3 months of treatment, allopurinol healed 93% and dimethyl sulfoxide healed 95% of the venous ulcers. The results suggest that oxygen-derived free radicals are directly implicated in the mechanism of venous ulceration and are responsible for its persistence. Scavenging such radicals stimulates the healing of ulceration.