Intraperitoneal administration of polar glycopeptidolipids extracted from Mycobacterium chelonae (pGPL-Mc) greatly increased the resistance of mice against a lethal disseminated Candida albicans infection. This enhanced resistance was demonstrated by an increase in the number of survivors and the prolongation of the mean survival time of animals following a lethal challenge. These effects were dependent upon the infective dose of Candida albicans, the dose of pGPL-Mc and the timing of its administration. This enhanced resistance was correlated with the development and persistence of a hyperleukocytosis, associated with a long lasting increase in the number of polymorphonuclear neutrophils. On the contrary, no candidacidal effect of the serum collected from pretreated mice was observed; suggesting that the ability of pGPL-Mc to increase resistance against Candida albicans infection is likely to be mediated by polymorphonuclear neutrophils. These results confirm previously described immunostimulating properties of pGPL-Mc and open the way for the evaluation of its effect in the prevention of opportunistic infections in neutropenic patients.