The activity of caspofungin (CFG) combined with amphotericin B (AMB) against azole-resistant Candida albicans was evaluated in vitro (chequerboard) and in vivo (murine). CFG+AMB resulted in positive interactive effects in vitro (fractional inhibitory concentration index 0.75). Compared with untreated controls, CFG+AMB prolonged mouse survival (P = 0.006) and compared with AMB alone, CFG+AMB prolonged mouse survival (P = 0.36); however, the latter difference was not significant. CFG+AMB treatment significantly reduced kidney cfu compared with untreated controls and CFG-treated groups (P < or = 0.05 for both comparisons). In addition, this combination reduced brain cfu significantly compared with untreated controls and AMB-treated mice (P = 0.005 and 0.05, respectively).