Antrodia cinnamomea Chang & Chou, sp. nov. growing rarely oil the inner wall of Cinnamomum kanehirai Hay was identified as a new species of Antrodia, which is an expensive folk medicine and used as an antidote, anticancer and anticnesmatic drug. In this study the influence of different physical and chemical factors on the growth of mycelium by A. cinnamomea CCRC35396 was investigated in submerged cultures of using shake flasks. In addition, response surface methodology (RSM) was also used to optimize medium composition for the enhancement of biomass productivity.The results indicate that when a submerged culture in shake flasks was operated at 25degreesC, initial pH 5 and rotation speed 100 rpm, the mycelium concentration reached 486.8 mg/100 ml at 14th day. High rotation speed was unfavorable to the growth of mycelium and the optimum was around 100 rpm. According to the RSM, optimal initial pH and the concentrations of C-source and N-source were determined and the mycelium concentration of A. cinnamomea rose to 2164.2 mg/100 ml at the 7th day and the biomass productivity had a eightfold increase, compared to the growth in basal medium. The results proved that the growth rate of mycelium of A. cinnamomea could be highly enhanced by means of the control of cultural conditions and the modification of medium compositions based on the RSM. (C) 2003 Elsevier Inc. All rights reserved.