The characteristics, progressivity and reversibility of the changes in glucose homeostasis brought about by chronic protein-calorie malnutrition were studied in the rat. Four-week-old male rats received a control diet (15% protein) or a low-protein diet (5% protein) until the age of 28 weeks. Other rats received the low-protein diet until 12-15 weeks, and then the control diet. In malnourished rats, fasting plasma glucose levels and both fasting and fed plasma insulin levels were lower than in control rats. At the age of 15 weeks, tolerance to oral glucose was slightly poorer, whereas tolerance to intravenous glucose was slightly better in rats receiving the low-protein diet than in control rats. During both tests the insulin response of malnourished rats was severely blunted. This inhibition largely exceeded the small decrease in their pancreatic insulin reserves. Similar results were obtained when the same test was repeated 9 weeks later. If the rats were transferred from a low-protein to a control diet for these 9 weeks, the changes in glucose tolerance were partially corrected, but the insulin response remained inhibited. Though hepatic glycogen stores were increased in malnourished rats, i.v. glucagon or arginine caused a smaller rise in plasma glucose levels than in control rats. The insulin response was also impaired and, unlike the glucose response, was not restored by 6 weeks on a control diet. The hypoglycaemia induced by intravenous insulin was more sustained in malnourished than in control rats, but this abnormality was corrected by refeeding a control diet for 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)