In yeast, the mRNA encoded by the MAT alpha 1 gene is unstable (t1/2 = 5 min) and the mRNAs encoded by the ACT1 gene (t1/2 = 30 min) and the PGK1 gene (t1/2 = 45 min) are stable. To understand the RNA structural features that dictate mRNA decay rates in yeast, we have constructed PGK1/MAT alpha 1 and ACT1/MAT alpha 1 gene fusions and analyzed the decay rates of the resultant chimeric transcripts. Fusion of a MAT alpha 1 segment containing 73% of the coding region and the 3' untranslated region to either of the stable genes is sufficient to cause rapid decay of the chimeric mRNAs (t1/2 = 6-7.5 min). Sequences required for this rapid decay are not found in the MAT alpha 1 3' untranslated region but are located within a 42-nucleotide segment of the coding region that has a high content (8 out of 14) of rare codons. Introduction of a translational stop codon upstream of this region stabilizes the hybrid mRNAs, indicating that the rapid decay promoted by these sequences is dependent on ribosomal translocation.