This article investigates heterogeneous proliferation within a seeded three-dimensional scaffold structure with the purpose of improving protocols for engineered tissue growth. A simple mathematical model is developed to examine the very strong interaction between evolving oxygen profiles and cell distributions within cartilaginous constructs. A comparison between predictions based on the model and experimental evidence is given for both spatial and temporal evolution of the oxygen tension and cell number density, showing that behaviour for the first 14 days can be explained well by the mathematical model. The dependency of the cellular proliferation rate on the oxygen tension is examined and shown to be similar in size to previous work but linear in form. The results show that cell-scaffold constructs that rely solely on diffusion for their supply of nutrients will inevitably produce proliferation-dominated regions near the outer edge of the scaffold in situations when the cell number density and oxygen consumption rate exceed a critical level. Possible strategies for reducing such non-uniform proliferation, including the conventional methods of enhancing oxygen transport, are outlined based on the model predictions. (C) 2005 Wiley Periodicals, Inc.