The effect of acute and chronic ethanol administration on DNA synthesis in the gastrointestinal tract of the rat was investigated. Acute intragastric ethanol administration (3 g/kg; 50%) decreased significantly in vivo DNA synthesis when measured 1 hour after alcohol application in the stomach and in the upper small intestine, whereas acute intravenous ethanol administration had no significant effect. In contrast, chronic ethanol ingestion resulted in a significant increase of in vivo and in vitro DNA synthesis in the upper gastrointestinal tract. In addition, even a more enhanced stimulation of DNA synthesis after chronic ethanol consumption was found in isolated intestinal cells. These results indicate an inhibition of gastrointestinal cell regeneration directly after the oral application of ethanol. The enhanced cellular regenerativity observed after chronic ethanol consumption may be secondary to the ethanol induced damage of the gastrointestinal tract.