The effect of subminimal inhibitory concentrations (MICs) of nystatin, amphotericin B, clotrimazole, miconazole and 5-fluorocytosine on the in vitro susceptibility of Candida albicans to physiological concentrations of apo-lactoferrin was investigated. Pre-exposure of C. albicans in 1:4 and 1:16 MICs of the antifungals resulted in an increased resistance to apo-lactoferrin-mediated cell death. Preincubation of Candida in tunicamycin (an agent that inhibits the synthesis of yeast cell-wall mannoproteins) and subsequent exposure to apo-lactoferrin enhanced the antifungal activity, whilst addition of ergosterol (a yeast cell-wall component) to the assay suspension had no significant effect. These results taken together indicate that apo-lactoferrin, an important component of saliva, interacts with cell-membrane constituents of C. albicans such as mannoproteins, and may modulate the effect of topical antifungal agents commonly prescribed for oral candidoses.