This paper addresses the optimization of supply chain design and planning under responsive criterion and economic criterion with the presence of demand uncertainty. The supply chain consists of multi-site processing facilities and corresponds to a multi-echelon production network with both dedicated and multiproduct plants. The economic criterion is measured in terms of net present value, while the criterion for responsiveness accounts for transportation times, residence times, cyclic schedules in multiproduct plants and inventory management. By using a probabilistic model for stock-out, the expected lead time is proposed as the quantitative measure of supply chain responsiveness. The probabilistic model can also predict the safety stock levels by integrating stock-out probability with demand uncertainty. These are all incorporated into a multi-period mixed-integer nonlinear programming (MINLP) model, which takes into account the selection of manufacturing sites and distribution centers, process technology, production levels, scheduling and inventory levels. The problem is formulated as a bi-criterion optimization model that maximizes the net present value and minimizes the expected lead time. The model is solved with the epsilon-constraint method and produces a Pareto-optimal curve that reveals how the optimal net present value, supply chain network structure and safety stock levels change with different values of the expected lead time. A hierarchical algorithm is also proposed based on the decoupling of different decision-making levels (strategic and operational) in the problem. The application of this model and the proposed algorithm are illustrated with two examples of polystyrene supply chains. (C) 2008 Elsevier Ltd. All rights reserved.