The protective effects of human saliva, known to contain various proteinaceous factors that have anti-Candida activity in vitro on oral candidiasis in the mouse model, were examined in vivo. Oral candidiasis was established by oral inoculation of viable Candida albicans (C. albicans) cells to ICR mice, 24 h after administration of predonisolone. These mice received orally 0.1 ml human saliva or sterile distilled water into the oral cavity a total of five times at specific intervals: 3, 6, 12, 24, and 36 h after inoculation. Seventy-two hours after inoculation with C. albicans, viable C. albicans cells in the oral cavity of the mice were counted and a subjective score for the extent of white patches on the tongue surface determined. The results showed that viable counts were significantly lower in the human saliva group than in the distilled water group (P < 0.05). Scores for white patches on the tongue were also significantly lower in the saliva group than in the distilled water group (P < 0.05). These results suggest that administration of human saliva may inhibit the colonization of the oral cavity by C. albicans in mice and the subsequent onset of oral candidiasis.