Therapy of selected human malignancies with interferon-α is widely accepted but often complicated by the emergence of interferon-α resistance. Interferon is a pleiotropic cytokine with antiproliferative, antitumour, antiviral and immunmodulatory effect; it signals through the Jak-STAT signal transduction pathway where signal transducer and activator of transcription 1 plays an important role. Here we report both, a lack of signal transducer and activator of transcription induction in interferon-α resistant renal cell carcinoma cells and signal transducer and activator of transcription 1 reinduction of phorbol 12-myristate 13-acetate-stimulated peripheral blood mononuclear cells supernatant. Preliminary experiments on the identification of the molecules that reinducing signal transducers and activators of transcription 1 indicate that interferon-γ may be the responsible candidate cytokine, but several others may be involved as well. This work provides the basis for therapeutic strategies directed at the molecular modulation of interferon-α resistance in human neoplasms.