CD30 ligand (CD30L), but not its cognate receptor CD30, is frequently expressed on acute myeloid leukaemia (AML) blasts. In the present study, we found that leukaemic blasts presenting surface CD30L displayed a characteristic cytokine-receptor pattern that makes them ideal targets for those cytokines usually produced by Th2-type cell subsets. In particular, even though a broad distribution of Th2 cytokine receptors by AML blasts was shown, we demonstrated the almost exclusive expression of interleukin 4 (IL-4) receptor (R), in the absence of its cognate cytokine, by CD30L+ AML. Furthermore, a number of Th2-associated markers, including CD30, IL-4 and GATA-3, were expressed by residual T cells derived from CD30L+ AML but not from CD30L- AML, in which the presence of the Th1-associated marker LAG-3 was documented in some cases. The production of IL-4 in the absence of interferon gamma (IFN-gamma) was also detected in CD3+/CD30+ T cells from CD30L+ AML. These results, along with the shift toward IL-4-producing specific T-cell clones observed in CD30L+ AML samples by enzyme-linked Immunospot (ELISpot) assay, were consistent with the hypothesis of a Th2 polarization taking place in T cells from CD30L+ AML. The notion that IL-4 was able to enhance in vitro proliferation of CD30L+/IL-4R+ purified leukaemic blasts suggests that the selective interaction of IL-4-producing CD30+ T cells with CD30L+ leukaemic progenitors may have a role in the progression of this particular AML subset.