Interferon is widely used as the most effective agent in the adjuvant therapy of patients with melanoma. However, little is known about the effect of intermediate dose interferon (IDI) in adjuvant therapy. We conducted this study to determine whether intermediate doses of interferon-alpha 2 could be beneficial for these patients. A series of 84 melanoma patients with high-risk relapse potential (stage II-III) after excisional biopsy were enrolled for adjuvant therapy with IDIs, either IFN-alpha 2a, 9 MU or IFN alpha 2b, 10 MU per day, subcutaneously, for 1 yr consisted of an induction period (5d/wk for 4 wk) followed by 48 wk of same dose administered three times per week. The median follow-up was 25.9 mo with range 4-90.4 mo. Thirty-three (39%) patients had progressed; 18 (55%) of them while on treatment. The median (range) time of the failure occurrence was 9.1 mo (1.7-47.3 mo). Distribution of failure site was identical and the majority of the recurrences were found as single metastasis. For distant metastasis-free interval, mean (+/- SE) value was 28.8 +/- 3.6 mo: 1- and 2-yr survival rates were 87.8 +/- 5.7% and 61.6 +/- 9.3%, respectively. Twenty-two deaths were observed. Five-year survival rates of progression-free survival and overall survival were 50% and 60%, respectively. Generally, the treatment was found well-tolerated; drug-induced dose reduction or treatment discontinuation due to toxicity was minimal. Severe toxicity was rare. In conclusion, the small number of patients and the short follow-up does not permit any conclusion. However, the preliminary data seem to show that treatment with IDI was usually well tolerated with low toxicity of the patients during the adjuvant therapy.