To evaluate the metabolic consequences of short-term (i.e., less than 24 hours) starvation, glucose and fat metabolism were studied in eight healthy subjects and in eight patients with stable cirrhosis after 16-hour and again after 22-hour starvation by 3-[3H]glucose and [14C]palmitate turnover and by indirect calorimetry. Although patients and controls showed significant increases in free fatty acid concentration (respectively, 48% +/- 12% and 53% +/- 17%) and turnover (55% +/- 14% and 71% +/- 21%) during short-term starvation, the values after 16- and after 22-hour starvation were higher in cirrhosis. Fat oxidation was enhanced in the patients, but did not increase during fasting in contrast to controls (increase 19% +/- 17%, P less than 0.05). Net glucose oxidation was decreased in postabsorptive cirrhotics (P less than 0.05). Although postabsorptive glucose turnover was not different from controls, starvation induced a greater decrease in glucose turnover in the patients (25% +/- 3% vs. 10% +/- 3%, P less than 0.05). This was not reflected in plasma glucose concentrations. In conclusion, the effects of starvation on glucose and fat metabolism are enhanced in cirrhosis; fasting hypoglycemia is prevented by decreased use of glucose. It remains to be established whether these changes are merely explained by defective liver function, per se.