Statistically based experimental designs were used to optimize the medium for meilingmycin (MLM) production by Streptomyces nanchangensis M-6. In the first optimization step the effects of corn flour, maize starch, soybean meal, yeast meal, K2HPO4, KNO3, soybean oil, NaCl and CaCO3 on MLM production were evaluated by using a fractional factorial design. The production of MLM was favored by using corn flour or maize starch, but adversely affected by higher level of yeast meal. Other components exerted no significant influence on MLM production. The path of the steepest ascent was used to access the optimal region of the medium composition. In the third step, the concentrations of corn flour and maize starch were further optimized with central composite design and response surface analysis. This optimization strategy led to the enhancement of MLM production from 51.3 to 228.5 mu g/mL. (c) 2005 Elsevier Ltd. All rights reserved.