Since their first use at the clinic almost 30 years ago. interferons (IFNS) have become an accepted therapy in a range of malignancies. Although IFN All induce remissions in some patients, they are of no benefit, or at best, lead only to minor improvements in the great majority of patients. This review considers possible mechanisms underlying the antitumour effects of IFN, and discusses possible reasons for resistance to IFN therapy in patients with malignant disease.