Vascular and immunological mechanisms are both likely to be involved in heatstroke, this condition being preceded by a decrease in cerebral blood flow and an increase in brain cytokine concentrations. As the two mechanisms involve a nitridergic step, we analysed their respective role in heat tolerance by exposing vigil rats to heat after treatment with nitric oxide synthases (NOS) antagonists: non-specific inhibitors N-omega-nitro-L-arginine (LNA) and N-nitro-L-arginine-methyl-ester (L-NAME); 7-nitroinclazol (neuronal NOS inhibitor) and aminoguanidine (AG) (inducible NOS inhibitor). Heat exposure was interrupted when clinical signs occurred or when colonic temperature reached 43 degreesC. LNA and L-NAME dramatically reduced heat tolerance, while AG did not modify it. These results suggest the involvement of constitutive NOS in heat tolerance. Inducible NOS does not seem to be involved in the occurrence of heatstroke. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.