Background The mechanisms of action for volatile anesthetics remain unknown for centuries partly owing to the insufficient or ineffective research models. We designed this study to develop three strains derived from a wild-type Drosophila melanogaster with different sensitivities to volatile anesthetics, which may ultimately facilitate molecular and genetic studies of the mechanism involved.Methods Median effective doses (ED50) of sevoflurane in seven-day-old virgin female and male wild-type Drosophila melanogaster were determined. The sensitive males and females of percentile 6-10 were cultured for breeding sensitive offspring (S1). So did median ones of percentile 48-52 for breeding median offspring (M1), resistant ones of percentile 91-95 for breeding resistant offspring (R1). Process was repeated through 31 generations, in the 37th generation, S37,M37 and R37 were used to determine ED50 for enflurane, isoflurane, sevoflurane, desflurane, halothane, methoxyflurane,chloroform and trichloroethylene, then ED50 values were correlated with minimum alveolar concentration (MAC) values in human.Results From a wild-type Drosophila melanogaster we were able to breed three strains with high, median and low sevoflurane requirements. The ratio of sevoflurane requirements of three strains were 1.20:1.00:0.53 for females and 1.22:1.00:0.72 for males. Strains sensitive, median and resistant to sevoflurane were also sensitive, median and resistant to other volatile anesthetics. For eight anesthetics, ED50 values in three strains correlated directly with MAC values in human.Conclusions Three Drosophila me/anogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED50 are directly correlated with MAC in human for eight volatile anesthetics.