Spontaneously arising transplantable T cell lymphoma, designated as Dalton's lymphoma (DL), is characterized by a highly invasive and deleterious nature almost completely paralysing the host immune system. The level of interleukin (IL)-13 is elevated in serum and ascitic fluid of the DL-bearing host. IL-13 is a potent immunosuppressive cytokine and is an alternative activator of macrophages that suppresses the production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS), and proinflammatory cytokines. The expression of iNOS and proinflammatory cytokines are dependent largely upon the activation of nuclear factor-kappaB (NF-kappaB). Activation of NF-kappaB involves the degradation of cytoplasmic inhibitor IkappaBalpha, allowing the nuclear translocation of NF-kappaB and thereby transcription of the iNOS gene. Therefore, in this study we sought to determine whether the alternative activation or type II polarization of macrophages induced by IL-13 is mediated by the suppression of NF-kappaB and cytoplasmic preservation of IkappaBalpha. Western blot analysis and electrophoretic mobility shift assay (EMSA) indicate that tumour-associated macrophages (TAM) or polarized type II macrophages are due to preserved protein expression of IkappaBalpha, and therefore suppressed NF-kappaB nuclear translocation. These findings suggest that IL-13 may operate through the suppression of NF-kappaB activation and preservation of IkappaBalpha.