D-ribose was given orally and/or intravenously to nine healthy subjects at doses ranging from 83.3 to 222.2 mg/kg per hour for at least four hours. The serum ribose level increased in a dose-dependent manner to maximum concentrations of 75 to 85 mg/dl. The serum glucose level decreased after the beginning of continuous ribose administration and was reduced as long as ribose was being administered. The oral or intravenous administration of 166.7 mg/kg per hour of ribose resulted in a 25% decrease in serum glucose. Higher intravenous doses of ribose did not provoke a further decrease in serum glucose concentration. Oral administration of 166.7 mg/kg per hour led to an increase in serum insulin concentrations from a mean of 8.4 (range 6.4-11.5) to 10.4 (range 6.3-15.4) microU/ml (p less than 0.05). In contrast, intravenous administration did not change serum insulin concentrations significantly. The serum c-peptide concentration remained unchanged regardless of treatment. We conclude that the variations in plasma insulin concentrations do not account for the observed decrease in mean serum glucose concentrations accompanying D-ribose administration.