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Although it is an established concept that the liver is important in the disposition of glucose, the quantitative contribution of the splanchnic and peripheral tissues, respectively, to the disposal of an oral glucose load is still controversial. In the present investigation, we have employed the hepatic venous catheter technique in combination with a double-tracer approach (in which the glucose pool is labeled with 3H-glucose and the oral glucose load is labeled with 14C-glucose) to quantitate the four determinants of oral glucose tolerance: rate of oral glucose appearance, splanchnic glucose uptake, peripheral glucose uptake, and suppression of hepatic glucose production. Studies were carried out in 11 normal volunteers in the overnight-fasted state and for 3.5 h after the ingestion of glucose (1 g/kg body wt; range, 55-93 g). In the postabsorptive state, the rate of endogenous (hepatic) glucose production, evaluated from the 3H-glucose infusion, was 2.34 +/- 0.06 mg/min X kg. Glucose ingestion was accompanied by a prompt reduction of endogenous glucose output, which reached a nadir of 0.62 +/- 0.23 mg/min X kg at 45 min and remained suppressed after 3.5 h (0.85 +/- 0.22 mg/min X kg). The average inhibition of hepatic glucose output during the absorptive period was 53 +/- 5%. The appearance of ingested glucose in arterial blood, as derived from the 14C-glucose measurements after correction for recycling 14-C radioactivity, reached a peak after 15-30 min, and 14C-glucose continued to enter the systemic circulation throughout the observation period. The rate of appearance of ingested glucose was 2.47 +/- 0.45 mg/min X kg at 3.5 h. A total of 73 +/- 4% of the oral load was recovered in the systemic circulation within 3.5 h.(ABSTRACT TRUNCATED AT 250 WORDS)