This study formulates a model to maximize the profit of a lignocellulosic biofuel supply chain ranging from feedstock suppliers to biofuel customers. The model deals with a time-staged, multi-commodity, production/distribution system, prescribing facility locations and capacities, technologies, and material flows. A case study based on a region in Central Texas demonstrates application of the proposed model to design the most profitable biofuel supply chain under each of several scenarios. A sensitivity analysis identifies that ethanol (ETOH) price is the most significant factor in the economic viability of a lignocellulosic biofuel supply chain. (C) 2011 Elsevier Ltd. All rights reserved.