T lymphocytes from patients with renal cell carcinoma (RCC) show reduced immune function and impaired activation of the transcription factor, NF-κB. We determined the mechanism of NF-κB suppression in T cells of RCC patient and determined whether supernatant fluid from RCC explants (RCC-S) induced the same phenotype of NF-κB suppression in normal T cells that is observed in patient T cells. The pattern of κB-binding activity in T cells of RCC patient was altered as compared to that seen in T cells obtained from normal volunteers. In some patients, no activation of RelA/NFkappaB1-binding activity was detectable, while in others κB-binding activity was modestly induced but the duration was reduced. IκBα was degraded normally following stimulation in both normal controls and T cells from RCC patients. RCC-S did not alter the cytoplasmic levels of RelA and NF-κB1 but did suppress their nuclear localization and inhibited the activation of RelA/NF-κB1 binding complexes. These results show that RCC-S can induce in normal T cells the same phenotype of impaired NF-κB activation that is detected in T cells of RCC patient. It also appears that NF-κB suppression by RCC-S may contribute to the immunosuppression of host immunity.