1. Seventeen healthy male subjects were studied after an overnight fast (12-14 h) and for 3 h after ingestion of 75 g glucose to investigate peripheral glucose metabolism (uptake, oxidative and nonoxidative metabolism) using the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. In normal subjects, during the 3-h study period, 30.3 +/- 2.1 g (40.4% of the ingested load) of glucose were processed by skeletal muscle in the body as a whole and 8.1 +/- 0.6 g were completely oxidized while 22.2 +/- 2.3 g were utilized through the nonoxidative pathway in muscle tissue. 2. After ingesting 75 g of glucose, normal women showed greater glucose uptake per unit of muscle mass and a predominant tendency toward utilizing glucose by a nonoxidative pathway than did normal men. The higher glucose uptake of the female group and an insulin response not significantly different from that of the male group suggest that muscle insulin sensitivity is greater in normal women. 3. The study of the effects of 50 and 100 g glucose loads on the peripheral glucose metabolism of normal men revealed a dose-dependent metabolic response in muscle tissue to these oral glucose challenges with respect to forearm muscle glucose uptake and nonoxidative glucose metabolism. The oxidative responses of the muscle tissue were not directly proportional to the oral glucose loads. 4. The administration of carbohydrate, usually glucose, leads to a decrease in the serum level of inorganic phosphorus (Pi), attributed to Pi flow from the extracellular to the intracellular compartment as part of the increased glucose metabolism induced by insulin. However, our data indicate that muscle tissue is not the site responsible for the fall in serum Pi after glucose ingestion. 5. Spontaneous human hyperthyroidism increases glucose uptake by the forearm muscles in the postabsorptive state and during an oral glucose challenge, with increased fluxes of glucose through the oxidative and nonoxidative pathways. 6. The insulin resistance occurring in the presence of chronic growth hormone (GH) excess is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism. These probably are early derangements because they are also observed in acromegalic patients with normal glucose tolerance. 7. A clear-cut dissociation between peripheral glucose and potassium transport was observed in the forearm muscle of acromegalic patients.(ABSTRACT TRUNCATED AT 400 WORDS)