Flow cytometric analysis reveals that 5 human melanoma cell lines (M 14, IGR3, ME1477, JUSO, GLLI9) express both aand P chain of the interleukin 2 receptor (IL-2Ra and IL-2Rp). These chains are able to specifically bind IL-2 and to form high-affinity heterodimers (IL-2RaP). Analysis of poly At RNAs by Northern blot reveals the presence of typical transcripts for both the IL-2Ra gene (3.6 kb) and the IL-2Rp gene (4 kb). Reverse transcriptionlpolymerase chain reaction analysis allowed transcripts for the IURy (pa) gene to be detected in 3 of these melanoma cell lines (M14, IGR3, ME 1477). Incubation with human recombinant IL-2 modifies in IL-ZRa+P+y+ (M 14) the expression of several surface molecules: down-regulation of ICAM-I, HLA class I and HLA-DR and up-regulation of CD44. IL-2 is also active on IL-2atP+y-cell lines since it decreases ICAM-I and HLA class-ll expression at the surface of ]US0 cells. Down-regulation of ICAM-I, whose expression in melanoma cells is a marker of tumor progression, is detectable within 3 hr in MI4 cells and is maximal after 48 hr incubation, at IL-2 concentrations corresponding to the high-affinity heterodimers. This feature is specific since it is partially inhibited by MAbs directed against the IL-2 binding site of the IL-2Ra (MAR93, IOT14) and IL-2RP (MiKPI, TU27) chains. Our data support the notion of a direct effect of IL-2 on human melanoma cells. Modulation of the expression of surface molecules which is important for the interaction with irnrnunocornpetent cells or for tumor progression, could have a role to play during in vivo IL-2 treatment of human melanomas.