The sponge sterol 9alpha,11alpha-epoxycholest-7-ene-3beta,5alpha,6alpha,19-tetrol 6-acetate (ECTA) (1) is the first marine natural product to reverse fluconazole resistance mediated by a Candida albicans MDR efflux pump. The IC(50) of fluconazole is decreased from 300 to 8.5 microM (35-fold enhancement) when combined with 1(3.8 microM). A revised C-6 configuration of 1 is established.