A computational scheme using the Chimera grid method is presented for simulation of three-dimensional motion and aggregation of two red blood cells (RBCs) in a narrow tube. The cells are modelled as rigid ellipsoidal particles; the computational scheme is applicable to deformable fluid-filled particles. Attractive energy between two RBCs is modelled by a depletion interaction theory and used for simulating aggregation of two cells. Through the simulation, we show that the Chimera grid method is applicable to the simulation of three-dimensional motion and aggregation of multiple RBCs in a microvessel and microvascular network. Copyright © 2006 John Wiley & Sons, Ltd.