The relative potency of interferon alpha (IFN alpha), interferon beta (IFN beta), and interferon gamma (IFN gamma) in inducing the expression of HLA class I antigens, as well as their capacity to counteract the inhibition induced by glucocorticoid hormones on HLA class I antigen expression, were analysed in the human melanoma cell line M14, both at membrane and at mRNA level. The data obtained indicate that (a) IFN enhance with different potency (IFN gamma > IFN beta > IFN alpha) the expression of HLA class I antigens in M14 cells, (b) prednisone inhibits HLA class I antigen expression, (c) glucocorticoid hormones, when associated with IFN alpha or IFN gamma, inhibit the HLA class I enhancement induced by IFN alone, and, finally, (c) the association between 1 microM prednisone or 1 microM deflazacort and IFN beta seems to potentiate the enhancing capacity of IFN on the expression of HLA class I molecules at the mRNA level. These findings, if confirmed, might indicate that IFN and glucocorticoid hormones are not mutually exclusive in the management of human melanoma.