Experiments were conducted to evaluate the effects of amphetamine (0.4 mg/kg of body weight/day) on the development of oral candidiasis in Sprague-Dawley rats. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of Candida albicans infection. Treatment with drugs (placebo or amphetamine) was initiated 7 days before C. albicans inoculation and lasted until the end of the experiments, day 15 postinoculation. Establishment of C. albicans infection was evaluated by swabbing the inoculated oral cavity with a sterile cotton applicator on days 2 and 15 after inoculation, followed by plating on YEPD (yeast extract-peptone-dextrose) agar. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results show that amphetamine exacerbates C. albicans infection of the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by fungal hyphae were found in amphetamine-treated rats compared to those found in the rats injected with a placebo. The last two parameters increased in rats treated with the placebo compared to the parameters of the untreated control rats.