Ten patients with aggressive NHL who failed to achieve a complete remission with first-line chemotherapy were treated with Ara-C and alpha IFN. Ara-C was administered subcutaneously at 100 mg on day 1, 150 mg on day 2 and 200 mg on days 3, 4 and 5 of a 28 d cycle; alpha IFN was given at 3 million International Units three times a week and continued for 2 years in CR patients. Six CR were attained with a median duration of 36+ months. Toxicity was mild. A new approach to second-line therapy for aggressive NHL is proposed.