Skin lesions in mycosis fungoides (MF) and cutaneous-type adult T-cell leukemia/lymphoma (c-ATL) are sometimes difficult to differentiate. Our previous investigations showed that the alpha-chain of interleukin-2 receptor (IL-2R alpha) secretion is enhanced in both acute and chronic type ATL. This finding suggested increased levels of IL-2R alpha in c-ATL that might differentiate it from MF. In this study, we report several observations on IL-2R alpha levels in MF and c-ATL. 1) Plasma levels of IL-2R alpha determined by enzyme-linked immunosorbent assay were higher in patients with c-ATL (tumor group, 17,571 +/- 5,919 U/ml; non-tumor group, 4,546 +/- 1,788 U/ml) than those of patients with MF (tumor group, 2,352 +/- 861 U/ml; plaque group, 530 +/- 174 U/ml). 2) The percentages of IL-2R alpha-positive cells in skin lesions of c-ATL were 30.5 +/- 13.4% in the non-tumor group and 62.7 +/- 12.0% in the tumor group, which were significantly higher than those of MF, plaque group (12.7 +/- 5.9%), and tumor group (3.4 +/- 2.3%). 3) Further, there was a significant correlation between plasma IL-2R alpha levels and the number of IL-2R alpha-positive cells in skin lesions in patients with c-ATL (r = 0.654, p < 0.0001) and MF (r = 0.537, p < 0.01) on an individual basis; whereas no increased IL-2R alpha levels in peripheral blood mononuclear cells were observed in patients with either MF or c-ATL. 4) Skin lesions of c-ATL had much higher levels of IL-2R alpha genomic RNA than those of MF in their initial stages when measured by DNase/reverse transcription/polymerase chain reaction and liquid hybridization analysis. These findings suggest that increased plasma IL-2R alpha levels in patients with either MF or c-ATL may be linked to cellular IL-2R alpha levels in the skin lesions, and thus reflect the difference between MF and c-ATL.