Up to now a number of studies have been performed to determine whether the combined use of cytokines and monoclonal antibodies (MAbs) directed against tumor-associated antigens (TAA) can increase the sensitivity of radioimmunoscintigraphy (RIS). It is well known that human natural and recombinant interferons can enhance the cell surface expression of HLA Class I and II antigens as well as some specific tumor antigens, but there is scanty and conflicting information about the expression and shedding of TAA. Some authors reported that alpha-IFN enhances the expression of a melanoma-associated antigen (MAA), recognized by conventional antiserum. Other authors have found no changes in the expression of MAA identified by MAbs. In a pilot study on patients with malignant melanoma Rosenblum demonstrated an increase in tumor uptake of the anti-melanoma MAb 96.5 after IFN administration. In our study we performed immunoscintigraphy with the anti-melanoma MAb 225.28S in the same patient before and after IFN administration in different doses. We point out the difference in biodistribution in different organs and in blood clearance and discuss the possibility to improve the sensitivity of RIS.