A controlled-environment membrane model for use in vitro was developed and employed in an attempt to mimic the environment of the vagina in order to study yeast-vaginal cell adhesion. Adhesion in vitro of four strains of Candida albicans (NIH 3181A, NIH 526B, ATCC 18804, and MCO 2400) to vaginal epithelial cells (VEC) appeared to be affected by the pH and the level of carbon dioxide that have been found to be present in the vagina in vivQ. Strain 3181A had a greater adhesion ability than 526B when the concentration of yeast cells was increased and when the yeast cells were incubated with VEC at pH 5 in sodium phosphate buffer in ambient air supplemented with 10%, CO2. Of the four strains of C. albicans used, 3181A had the greatest adhesion ability, with strains 2400, 18804, and 526B ranked in order of decreasing adhesion ability. Also, an enhanced, electron-dense, matted outer region of the cell walls of the yeasts was observed frequently when they were incubated in ambient air supplemented with 10% CO2. In addition, of the vaginal cells that had yeast cells attached to them, an average of 94.4% of the total yeast cells were attached to the microridge side of the VEC, whereas an average of only 5.6% of the total were found on the nonmicroridge side of the VEC. The results from this study indicate that adhesion of C. atbicans to the VEC surface was affected by the strain of yeast used, by the side of the vaginal cell exposed, and by the pH and CO2 levels present in the adhesion assay.