Current understanding of mRNA metabolism in animal cells is based largely on information concerning the highly abundant mRNAs found in specific types of highly differentiated cells. However, most of the active genes within a cell specify transcipts that are present at relatively low abundance and code for proteins required by all types of cells. The research proposed here focuses attention on the metabolism of an ubiquitous mRNA that codes for dihydrofolate reductase (DHFR), an enzyme found in all cells and required for the de novo biosynthesis of thymidylate (MTX)-resistant cells in which the abundance of DHFR protein, mRNA, and genes is as much as 500-fold greater than normal. All of the amplified DHFR genes are apparently active and subject to control by the same physiological parameters controlling DHFR gene expression in normal cells. Proposed experiments will enable us to answer the following questions concerning DHFR mRNA metabolism. Is the amount of DHFR mRNA released into the cytoplasm always proportional to the level of DHFR RNA in the nucleus? What percentage of DHFR coding region transcripts are converted to mRNA and how does this value change in response to growth stimulation, polyoma infection, or elevated cyclic AMP levels? If coding region sequences (i.e., exons) are degraded in the nucleus, how is this process carried out and how is it regulated? How are multiple DHFR mRNAs generated? What is the biochemical basis of DHFR mRNA degradation?