Adsorption of the cationic lipid dioctadecyldimethylammonium bromide (DODAB) onto bacterial cells changed the sign of the cell surface potential from negative to positive with a clear relationship between positive charge on bacterial cells and cell death [1]. Regarding the mechanism of DODAB action, neither bacterial cell lysis nor DODAB vesicle disruption took place [2]. The literature on antimicrobial action by cationic lipids and surfactants was comprehensively reviewed recently [3, 4]. In this work, the compared effect of the double- and single-chained compounds, DODAB and hexadecyltrimethylammonium bromide (CTAB), respectively, over a range of CTAB or DODAB concentrations, on Candida albicans or erythrocytes was evaluated by determining adsorption isotherms onto C. albicans cells, cell viability, electrophoretic mobility (EM) and leakage of small phosphorylated compounds, proteins and DNA from fungus or haemolysis from erythrocytes. High affinity, langmuirian adsorption isotherms for CTAB and DODAB bilayer fragments (BF) present a limiting adsorption of 7.8 and 3.7×10⁹ molecules per cell, respectively. For negatively charged C. albicans cells, cell viability is high whereas, for positively charged ones, it is low. At 50 % of fungus viability, EM is zero and concentrations for cationic compounds are 0.3 and 0.01 mM CTAB and DODAB, respectively. Thus, cells start to die well below the critical micelle concentration for CTAB, suggesting that cell lysis does not play a significant role in the mechanism of antifungal action. Indeed, there is no CTAB or DODAB induced leakage of tested compounds from the inner compartment of C. albicans cells over a broad range of amphiphile concentrations where cell viability is low. In contrast to the robust character of the fungus cells, erythrocytes are fragile in the presence of the cationic amphiphiles and, under isotonic conditions, suffer cationic amphiphile-induced haemolysis over a range of low DODAB (above 0.01 mM) and CTAB (above 0.001 mM) concentrations. The critical phenomenon determining fungus cell death and the antifungal effect of cationic surfactants and lipids is not cell lysis but rather the reversal of cell surface charge from negative to positive.