The optimization of critical medium components for the production of ethanol from cellulose by Clostridium thermocellum SS19 in anaerobic submerged fermentation was carried out using response surface methodology (RSM) based on central composite rotatable design (CCRD). The design contains a total of 54 experimental trials with the first 32 organized in a fractional factorial design and from 33 to 40 and 51 to 54 involving the replications of the central points. The design was employed by selecting filter paper, corn steep liquor, cysteine hydrochloride, magnesium chloride and ferrous sulphate as model factors. Among the five independent variables studied, all the nutrients were found significant, except magnesium chloride. The concentrations of filter paper, corn steep liquor, cysteine hydrochloride and ferrous sulphate in the medium, which have been found to be optimal for ethanol production, were 45, 8.0, 0.25, and 0.01 g/l, respectively. The organism produced 0.41 g of ethanol/g of the substrate consumed (81% yield efficiency) in the nutritionally optimized medium. The present study provides valuable information about the statistical optimization of media components for ethanol production from cellulosic biomass. (c) 2005 Elsevier Ltd. All rights reserved.