An extensive literature review on clinical trials and economic studies published on the use of IFN-alpha as adjuvant therapy in stage II - III (AJCC 1992) malignant melanoma was performed. Large clinical trials with sufficient follow-up were selected to assess the efficacy. Medico-economic studies, based on the results of several of these trials, were analysed to estimate the cost-effectiveness ratios of IFN in this disease. IFN-alpha demonstrated efficacy as adjuvant therapy in malignant melanoma with high-dose regimens in patients with overt regional nodal disease (so-called high-risk patients) and with low-dose regimens in stage IIA and -B patients without clinically detectable nodes (so-called intermediate risk patients). This efficacy was associated with high rates of severe side effects using a high-dose regimen. Based on these assumptions, economic analyses performed in different settings and using several methods to extrapolate clinical results are producing similar results of extra costs for IFN associated with a medical benefit. Incremental cost-effectiveness ratios provided are (< US dollars 50,000 per life year gained) in the range of current and widely used medical strategies in different diseases and settings. This should allow the recommendation of the use of IFN-alpha therapy in malignant melanoma, using high doses in high-risk patients and low doses in intermediate-risk patients. In the final decision of whether or not to treat, however, the patient has to be informed that IFN will probably only delay events, with the possibility of any curative effect being uncertain. This limited effect has to be balanced with the severe impact on quality of life of high-dose regimen and with the fact that many patients in whom low doses are indicated would not recur in the absence of treatment. It is also clear that patients with only a positive sentinel node are to be considered with the intermediate risk group in which they were evaluated.