The metabolic adaptations of peripheral muscle during a 5-day "modified" fast (daily oral intake of 200 g of glucose) were studied in 12 normal males. The volunteers were studied initially after receiving a balanced 2,400-kcal diet for at least 3 days (S1) and then after 5 days of modified fast (S2). The forearm muscle exchange of energy substrate (glucose) and the carbohydrate and lipid oxidation rates in muscle were measured during the postabsorptive state (S1) and after an oral glucose challenge (S2). 2. Glucose intolerance was not observed in either situation. Arterial glucose levels increased from a basal value of 83 mg/100 ml to 171 mg/100 ml in S1 and to 187 mg/100 ml in S2 at 30 and 60 min, respectively, and returned to basal values at 180 min in both studies. Increased forearm glucose uptake was observed in S2 compared to S1 (121.7 +/- 17.1 vs 92.6 +/- 12.0 mg 100 ml forearm-1 3 h-1), with decreased glucose oxidation (23.8 +/- 3.7 vs 30.4 +/- 4.7 mg 100 ml forearm-1 3 h-1) and increased glucose storage (98.0 +/- 16.6 vs 62.2 +/- 10.8 mg 100 ml forearm-1 3 h-1) as muscle glycogen. 3. Basal serum free fatty acid (FFA) levels were significantly more elevated in S2 than S1 (1030 +/- 95 vs 657 +/- 59 mumol/l; P less than 0.05) but were markedly reduced by glucose ingestion in both studies (352 +/- 33 (S2) vs 364 +/- 30 (S1) mumol/l at 120 min). Basal FFA oxidation was similar in both studies (0.091 +/- 0.015 (S1) vs 0.105 +/- 0.019 (S2) mg 100 ml forearm-1 min-1) and decreased significantly 3 h after glucose ingestion only in S1 (0.030 +/- 0.010 (S1) vs 0.078 +/- 0.020 (S2) mg 100 ml forearm-1 min-1; P less than 0.05). 4. The insulin response to oral glucose was similar in both studies (11,060 +/- 899 (S1) vs 11,078 +/- 918 (S2) microU ml-1 3 h-1), but the peak concentration occurred later (60 min (S2) vs 30 min (S1] and basal levels were significantly lower in S2 compared to S1 (9.2 +/- 1.7 vs 11.1 +/- 1.5 microU/ml; P less than 0.05). 5. These data show that the metabolic adaptations of normal subjects to a 5-day "modified" fast (daily oral intake of 200 g glucose) were increased muscle uptake of glucose, with reduced glucose oxidation and increased glucose storage in the form of muscle glycogen.