Calmodulin (CaM) is a calcium ion-binding protein that regulates a variety of cellular functions through its downstream target proteins. Previous studies have reported that overexpression of CaM enhances tolerance to stress, including resistance to salt, heat, cold, drought and plant pathogens. In this study, the growth of Cryptococcus humicola was inhibited by the CaM inhibitor, trifluoperazine, under aluminum (Al) stress. The expression of CaM of C. humicola (ChCaM) was upregulated when the concentration and treatment time with Al was increased. These results indicate that Al stress affects the transcription and translation of ChCaM and that ChCaM may play an important role in Al tolerance. Transgenic ChCaM Saccharomyces cerevisiae was constructed and designated as Sc-ChCaM. The ability of Sc-ChCaM to develop resistance to Al was significantly higher than that of control yeast containing the empty vector pYES3/CT designated as Sc. The residual Al content in the medium containing ChCaM transgenic yeast in culture was significantly lower than the initial amount of Al added in the medium or the residual Al content in the medium containing the control yeast in culture. This finding suggests that ChCaM confers Al tolerance in transgenic yeast, and the absorption of active Al from the culture may be one reason for Al tolerance. These results indicate that ChCaM may be a candidate gene for Al tolerance in engineered plants. (C) 2016, The Society for Biotechnology, Japan. All rights reserved.