Abstract: BACKGROUND: Translational efficiencies in Saccharomyces cerevisiae vary from transcript to transcript by approximately two orders of magnitude. Many of the poorly translated transcripts were found to respond to the appropriate external stimulus by recruiting ribosomes. Unexpectedly, a high frequency of these transcripts showed the appearance of altered 5' leaders that coincide with increased ribosome loading. RESULTS: Of the detectable transcripts in S. cerevisiae, 8% were found to be underloaded with ribosomes. Gene ontology categories of responses to stress or external stimuli were overrepresented in this population of transcripts. Seventeen poorly loaded transcripts involved in responses to pheromone, nitrogen starvation, and osmotic stress were selected for detailed study and were found to respond to the appropriate environmental signal with increased ribosome loading. Twelve of these regulated transcripts exhibited structural changes in their 5' transcript leaders in response to the environmental signal. In many of these the coding region remained intact, whereas regulated shortening of the 5' end truncated the open reading frame in others. Colinearity between the gene and transcript sequences eliminated regulated splicing as a mechanism for these alterations in structure. CONCLUSION: Frequent occurrence of coordinated changes in transcript structure and translation efficiency, in at least three different gene regulatory networks, suggests a widespread phenomenon. It is likely that many of these altered 5' leaders arose from changes in promoter usage. We speculate that production of translationally silenced transcripts may be one mechanism for allowing low-level transcription activity necessary for maintaining an open chromatin structure while not allowing inappropriate protein production.