A screening experiment with fractional factorial design and response surface methodology (RSM) with Box-Behnken design (BBD) was used to optimize the microwave-assisted extraction (MAE) of Yuanhu Zhitong (YZ) prescription. The optimum operating conditions were finally obtained by using a desirability function. A 2(6-2) fractional factorial design was initially employed and it was found that microwave power, extraction time, ethanol level and extraction times were the most important variables that affected the yield of tetrahydropalmatine, imperatorin and isoimperatorin, which are active components in YZ prescription. Results show that the optimal conditions were microwave power of 500W, ethanol level of 70% and extraction time was 27 min. The extraction yield of tetrahydropalmatine, imperatorin and isoimperatorin was 85.4%, 104.0% and 113.6%, respectively, and the yield of extracta sicca was 10.4%. (C) 2008 Elsevier B.V. All rights reserved.