The half-life of individual mRNA plays a central role in controlling the level of gene expression. However, the determinants of mRNA stability have not yet been well defined. Most previous studies suggest that mRNA length does not affect its stability. Here, we show significant negative correlations between mRNA length and stability in human and Escherichia coli, but not in Saccharomyces cerevisiae or Bacillus subtilis. This finding suggests the possibility that endonucleolytic attacks by RNA endonuclease and/or mechanical damage may strongly influence mRNA stability in both prokaryotes and eukaryotes.