Background: Although submerged fermentation (SmF) is the conventional method in industry, use of low-cost agro-residues for α-amylase production in SmF has not been well established. Here we optimized agro-residue-based medium and culture conditions for α-amylase production in SmF using a hyper-producing Bacillus subtilis KCC103. Results: B. subtilis KCC103 produced α-amylase in SmF by utilizing agro-residues. Wheat bran (WB) and sunflower oil cake (SFOC) were selected as the best substrates using shake flasks. Medium containing WB (carbohydrate rich) and SFOC (rich in protein and free amino acids) at 1 : 1 (w/w) ratio produced high levels (90 IU mL-1) of α-amylase at 30-36 h in a shake flask. The α-amylase yield was 14-fold enhanced (1258 IU mL-1) by optimizing process parameters and medium composition following response surface methodology in a bioreactor. The optimal conditions were:WB 1.27%, SFOC 1.42%, pH 7, 37 °C and 10-12 h. Both in shake flask and bioreactor a-amylase synthesis was not repressed by the release of simple sugars into the medium. Conclusion: KCC103 with catabolite derepression and hyperproducing ability is useful for economic α-amylase production using low-cost agro-residual substrates in conventional SmF. Since the production time (10-12 h) is much shorter than other strains this would improve productivity and further reduce the cost of α-amylase production. © 2008 Society of Chemical Industry.