Translation is a central cellular process in every organism and understanding translation from the systems (genome-wide) perspective is very important for medical and biochemical engineering applications. Moreover, recent advances in cell-wide monitoring tools for both mRNA and protein levels have necessitated the development of such a model to identify parameters and conditions that influence the mapping between mRNA and protein expression. Experimental studies show a lack of correspondence between mRNA and protein expression profiles. In this study, we describe a mechanistic genome-wide model for translation that provides mapping between changes in mRNA levels and changes in protein levels. We use our model to study the system in detail and identify the key parameters that affect this mapping. Our results show that the correlation between mRNA and protein levels is a function of both the kinetic parameters and concentration of ribosomes at the reference state. In particular, changes in concentration of free and total ribosomes in response to a perturbation; changes in initiation and elongation kinetics due to competition for aminoacyl tRNAs; changes in termination kinetics; average changes in mRNA levels in response to the perturbation; and changes in protein stability are all important determinants of the mapping between mRNA and protein expression. (C) 2003 Wiley Periodicals, Inc.