It has been well demonstrated that heat stress response (HSR) plays a crucial role in protecting cells from injury induced by various pathological stimuli. However, the protective mechanism of HSR is only poorly understood. The object of this article was to further investigate the relationship between the protective role of heat stress response and activation of NF-kappa B in primary cultured rat cerebellar granule cells. Heat stress was induced by hyperthermia (43+/-0.5 degrees centigrade), and DNA binding activity of NF-kappa B was determined with electrophoretic mobility shift assay (EMSA). Neuroapoptosis was measured by Hoechst 33258, agarose gel electrophoresis and flow cytometry (FCM) analysis. The results showed that the neurons treated with low potassium for l6 h could induce neuroapoptosis and promote the activity of nuclear kappa B. Heat stress treatment for 30, 60 and 90 min could suppress neuroapoptosis and the activity of nuclear kappa B induced by low potassium in a time-dependent manner. Activation of NF-kappa B using 100 nmol/L phorbol 12-myristate l3-acetate (PMA) could promote antiapoptotic action of heat stress response. In contrast, when NF-kappa B activation was inhibited by 10 micromol/L pyrrolidine dithiocarbamate derivatives (PDTC), heat stress did not provide protection against cell apoptosis induced by low potassium. The results suggest that the neuroprotection of heat stress has no relation to the suppression of NF-kappa B activity, and activation of NF-kappa B may promote antiapoptotic action of heat stress.