The murine translation initiation factor eIF4A is encoded by two genes: eIF4A(I), expressed in all mouse tissues, and eIF4A(II), a gene preferentially expressed in organs with low proliferative capacity. To investigate the hypothesis that regulation of the eIF4A isogenes is dependent upon cellular growth status, steady state expression of eIF4A(I) and eIF4A(II) mRNAs was quantitated in asynchronous cell populations and in cultures synchronized by nutrient starvation. Our data showed that changes in cell growth state were responsible for striking differences in eIF4A isogene-specific regulation. eIF4A(I) mRNA was 10-fold more abundant than eIF4A(II) in growing cells. In growth arrested cells eIF4A(I) mRNA levels remained unchanged, whereas eIF4A(II) mRNA levels increased approximately 3-fold. Following serum stimulation of growth arrested cells, eIF4A(I) mRNA levels increased 3- to 10-fold; conversely, eIF4A(II) mRNA levels decreased 2- to 3-fold. Thus, eIF4A(I) mRNA is synthesized and translated most efficiently in growing cells while eIF4A(II) mRNA synthesis and translation is associated preferentially with the growth-arrested (quiescent) state. This difference in expression patterns likely enables the cell to maintain required levels of this factor throughout its life cycle.