Acute and chronic ethanol ingestion causes a variety of pathological changes in the gastrointestinal tract, including gross morphological lesions and functional changes. We review whether these alterations also include changes in protein turnover, to explain the frequently observed villus atrophy and smooth muscle myopathy. The possibility that different regions of the gastrointestinal tract express diverse sensitivities is explored. Acute ethanol dosage profoundly reduced the synthesis of proteins in proximal regions of the rat gastrointestinal tract, but distal regions were less affected. In response to chronic ethanol exposure, similar regional sensitivities of the intestine were observed. In chronic studies the small intestine effects were characterised by selective losses of RNA, principally from the stomach and jejunum. We speculate whether the effects on protein synthesis were primarily due to ethanol or the consequence of acetaldehyde formation. We also determined whether changes in protein synthesis occurred secondary to alterations in nucleotide composition. The possible mediation by free-radical formation or impaired antioxidant status are also discussed. The overall results indicate that both acetaldehyde and ethanol are potent protein synthetic inhibitors and may contribute to the genesis of intestinal myopathy, possibly contributing towards motility disturbances and secondary malnutrition via malabsorption.