The cell wall mannan components of Candida albicans and Saccharomyces cerevisiae produced hyperthermic responses when injected intracerebroventricularly at doses of 10 microg in rats. Indomethacin treatment (5 mg/kg subcutaneously) completely abolished these responses. Serum interferon-gamma, tumor necrosis factor-alpha and interleukin-1beta levels showed an upward trend during the initial phase of the hyperthermic response induced by S. cerevisiae mannan. Meanwhile, serum levels of these proinflammatory cytokines did not increase at all at the initial phase of C. albicans mannan-induced hyperthermia. Histopathological examination of the brain tissue samples revealed no specific change throughout the parenchyma of rats given either mannan. These results indicate that the polysaccharide mannan components of yeasts, regardless of the pathogenicity, produce a pyrogenic response by a direct injection into the brain in rats. This response is not accompanied by proinflammatory cytokine induction in the periphery.