Adult T-cell leukemia (ATL) is an aggressive neoplasm of mature T cells. We aimed to ascertain the relationships between soluble CD25 (sIL-2R) and CD30 (sCD30) levels and nodal or extra-nodal involvement of ATL. Our study subjects were ATL patients whose sIL-2R and sCD30 levels were measured before initial therapy (n=32). Their sCD30 levels correlated significantly with the number of ATL cells in peripheral blood (PB) (ρ=0.456; P=0.009), while sIL-2R levels correlated significantly with the number of nodal lesions (ρ=0.660; P=0.001). We then also assessed the relationships of pulmonary lesions with the number of ATL cells in PB, lactate dehydrogenase levels, sIL-2R levels, and sCD30 levels in 24 patients whose pleural effusions and hilar lymphadenopathy were investigated before initial therapy. The results suggested that a high number of ATL cells in PB may be associated with pulmonary lesions. It is known that metalloproteinases shed and cleave cytokine receptors such as CD25 and CD30 from the cell surface as well as E-cadherin and extracellular matrix. It seems that serum levels of sIL-2R and sCD30 indicate the activation of metalloproteinases associated with ATL involvement in vivo.