Statistical experimental designs were used to optimize lovastatin production by culinary-medicinal oyster mushroom Pleurotus ostreatus OBCC 1031 under submerged fermentation. The Plackett-Burman design was used to determine effective culture parameters, glucose, lactose, maltose, glycerol, peptone, yeast extract, NH4SO2, NaCl, thiamine, and agitation speed. Statistical analyses of data from the Plackett-Burman design show that glucose, yeast extract, and agitation speed are significant parameters. The interactive effects of these culture parameters on lovastatin production by P. ostreatus OBCC 1031 were further studied by a Box-Behnken design. Maximum lovastatin production (114.82 mg/L) was reached after 6 days of fermentation in optimized culture conditions (30 g/L glucose, 10 g/L yeast extract, 200 rpm, 28 degrees C, and pH 6). This amount was found to be 50 times higher than that produced under unoptimized conditions in submerged fermentation by P. ostreatus.