Conflicting evidence has been reported on the metabolic fate of glucose following oral ingestion. We measured the metabolic pattern of gluconeogenic substrates as alanine, predominantly produced by muscle, and lactate after an oral glucose load in ten normal subjects and in eighteen non-insulin dependent diabetes mellitus (NIDDM) subjects. Neither in normal or NIDDM subjects were significant increases in plasma alanine observed, whereas a significant increase in plasma lactate was observed at 60, 90 and 120 min after a glucose load. Although a similar behaviour in plasma alanine and lactate between normal and NIDDM subjects was found, in NIDDM significantly higher levels of plasma alanine and lactate were found at each time. From these observations we conclude: 1) when glucose is ingested under post-absorptive conditions, since plasma alanine levels do not change concurrently with lactate increase, muscle tissue does not play a predominant role in glucose disposal 2) after an oral glucose load, the pattern of gluconeogenic precursors (alanine and lactate) is similar in normal and NIDDM subjects 3) the main cause of fasting and post-prandial hyperglycemia in NIDDM subjects may be due to an overproduction of alanine as well as lactate.