Dioctadecyldimethylammonium bromide (DODAB), a bilayer-forming synthetic amphiphile with antibacterial properties, also affects viability of Candida albicans. For C albicans, simultaneous determination of cell viability and electrophoretic mobility as a function of DODAB concentration yields a very good correlation between cell surface charge and cell viability. Upon increasing DODAB concentration, the cell surface charge decreases and changes its sign to yield positively charged cells. However, in contrast to the DODAB bactericidal property, the amphiphile effect on fungus over 1 h of interaction time is only fungistatic at 1 mM DODAB and ca. 10(6) cells/mL. Nevertheless, solubilization of fungicides in DODAB dispersions prepared by sonication causes complete loss of cell viability. Amphotericin B (AB) or miconazole (M) solubilization in the DODAB bilayer leads to 100% cell death, though the drug and DODAB effects are independent. Cell and DODAB bilayer membranes compete for AB or M solubilization with the amphiphile bilayer controlling drug release to the cell membrane. 0.1 mM DODAB plus AB or M concentration of 2 and 20 mug/mL, respectively, yielded 0% of cell viability for C albicans (2 x 10(6) cells/mL) over an interaction time of 24 h. The cationic liposomes by themselves yielded ca. 20% viability under similar conditions. The full potential of these cytotoxic cationic bilayers to control release and cytotoxicity of drugs remains hitherto unexplored.