Increased fasting hepatic glucose production is present in NIDDM patients, and has been shown to be due to increased gluconeogenesis. In order to determine the contribution of the cycling between glucose and three-carbon compounds (Cori and glucose-alanine cycles) to the increased hepatic glucose production, glucose kinetics measured overnight in seven obese NIDDM patients and six lean healthy subjects with both 6.6 2H glucose and U-13C glucose were determined. At 0500 h obese NIDDM subjects showed a 40% increase in glucose appearance calculated from 6.6 2H glucose, whereas glucose appearance calculated from U-13C glucose was similar compared to lean subjects, indicating increased glucose cycling. Non-oxidative glucose disposal was also increased three-fold in NIDDM patients. Glucose cycling was increased by 111% in NIDDM patients (118 +/- 18 mumole min-1 vs. 56 +/- 11 in controls, P < 0.05) and was positively correlated with plasma glucose concentration (r = 0.831, P < 0.001) and with non-oxidative glucose disposal (r = 0.714, P < 0.01). Four NIDDM patients were studied again after 3 days of insulin therapy. Insulin restored near-normoglycaemia (7.4 +/- 0.8 mmole l-1) and normalized rates of glucose appearance and glucose cycling. It is concluded that increased glucose cycling in obese NIDDM patients accounts for a major part of the increased fasting hepatic glucose production and non-oxidative glucose disposal in obese NIDDM subjects.