Following conventional surgical management, 100 patients with high risk Stage I melanoma were treated with transfer factor to reduce the incidence of disease recurrence. All patients had primary lesions invasive to Clark's level III or deeper and exceeding 1.0 mm in measured thickness. Ninety-six patients are available for analysis at 15 to 67 months (median: 30 months) after diagnosis. Nine patients have had a recurrence of disease (treatment failure), and one has died. Actuarial non-failure rate is 90%, and survival rate is 99% at five years. A nonrandomized but contemporary control group of 46 patients displaying comparable risk factors was treated with surgery alone. The non-failure rate of this group is 63%, and the survival rate is 69%, data consistent with the results of several published studies. These results suggest that transfer factor immunotherapy may be a valuable adjunct in the treatment of patients with high risk Stage I melanoma.