The degradation of messenger RNA in eukaryotic cells is initiated by endonucleolytic cleavage or by shortening of the poly(A) tail, which for some mRNAs activates a deadenylation-dependent decapping reaction. One type of rapid mRNA degradation in eukaryotes is caused by premature termination of translation. This turnover process prevents the translation of aberrant mRNAs, may affect the abundance and splicing pattern of nuclear transcripts, and may be involved in the aetiology of human genetic disease. Here we show that premature translational termination in yeast triggers decapping, independent of deadenylation, thereby exposing the transcript to 5'-to-3' degradation. Inactivation of the 5'-to-3' exonuclease reveals an additional 3'-to-5' pathway of mRNA turnover. These observations provide in vivo evidence for two new mechanisms of mRNA decay.