Earlier studies revealed that oral administration of lactoferrin (LF), a multi-functional milk protein, facilitated curing of dermatophytosis in guinea-pigs and man by an unknown mechanism. The present study aimed to assess the effect of feeding bovine LF on the host antifungal defence systems in guinea-pigs infected or immunised with Trichophyton mentagrophytes, a dermatophytosis-causing fungus. The unbound ironbinding capacity (UIBC) of the plasma of individual animals varied, and plasma with higher UIBC inhibited growth of T. mentagrophytes in vitro. However, LF administration did not enhance plasma UIBC or the anti-T. mentagrophytes activity of plasma in infected or uninfected animals. Phagocytic activity and reactive oxygen (RO) production of blood neutrophil polymorphonuclear leucocytes (PMNLs) were estimated by flow cytometry. LF administration caused no significant effects on phagocytic activity or RO production of neutrophil PMNLs in infected or uninfected animals. The functions of mononuclear cells (MNC) from the spleen were investigated in guinea-pigs immunised with heat-killed T. mentagrophytes conidia. The MNC were cultured with concanavalin A or inactivated T. mentagrophytes. In the bromo-deoxyuridine incorporation assay, the stimulation index was higher for MNC derived from LF-treated animals than for those from control animals. The culture supernates of MNC enhanced the ability of macrophages to kill T. mentagrophytes conidia. Furthermore, stronger augmentation was observed with the culture supernate from LF-treated animals than with that from control animals. In conclusion, LF feeding may potentiate the host antifungal defence systems by modulating MNC function rather than plasma antifungal activity or peripheral blood neutrophil PMNL activity.