The effects of glucose and insulin administration on splanchnic and leg exchange of glucose were investigated in seven patients with cirrhosis and six sex- and age-matched healthy controls using the catheter technique. After a basal period, glucose infusion (1 mg.kg-1.min-1) was given for 45 min, followed by a 2-h euglycemic insulin clamp (1 mU.kg-1.min-1). In the basal state insulin levels were significantly higher in patients than in controls (25 +/- 4 vs. 7 +/- 2 microU/ml). Net splanchnic glucose output tended to be lower in patients than in controls (0.50 +/- 0.16 vs 0.73 +/- 0.11 mmol/min nonsignificant), as did leg glucose uptake (0.06 +/- 0.01 vs 0.08 +/- 0.02 mmol/min, non-significant). Glucose infusion resulted in a significant rise in leg glucose uptake, while net splanchnic glucose output decreased in both groups. During the euglycemic insulin clamp, insulin concentrations rose to 110 +/- 10 and 80 +/- 8 microU/ml in patients and controls, respectively. C-peptide concentrations decreased in the healthy controls but were unchanged from the basal level in patients with cirrhosis. Glucose disposal during the last half hour of the clamp was 1.12 +/- 0.08 and 3.19 +/- 0.04 mmol/min in patients and controls, respectively (p < 0.001). Glucose was taken up by the splanchnic region in both groups but this uptake was significantly greater in patients than in controls (0.42 +/- 0.05 vs. 0.25 +/- 0.06 mmol/min, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)