Metabolic studies utilizing stable isotope tracer in humans have typically used intravenous tracer infusions and venous blood sampling. These studies explore subcutaneous infusion of isotope and "finger stick" capillary blood sampling to measure glucose turnover. Five subjects received simultaneous 8-h infusions of glucose labeled with isotope: [1-(13)C]glucose subcutaneously and [6,6-(2)H(2)]glucose intravenously. At regular intervals, venous and finger stick blood specimens were obtained. Finger stick blood was applied to filter paper. Substrate and isotopic steady state was reached after 7.0 h with both routes of infusion. The isotopic enrichments of finger stick and venous specimens did not differ significantly for the subcutaneously infused [1-(13)C]glucose (p = 0.33 and p = 0.23, respectively) but the finger stick [6,6-(2)H(2)]glucose enrichment was slightly higher (p < 0.03) than that of the venous sample. Using [6,6-(2)H(2)]glucose infusion and venous plasma sampling as the reference method, the [1-(13)C]glucose gave estimates of glucose R(a) that were 13% (plasma) and 17% (finger stick) lower (p < 0.001 and p < 0.02, respectively). This difference could be attributed to recycling of (13)C label. In conclusion, subcutaneous infusion and finger stick specimen collection onto filter paper represent a potential method of conducting in vivo studies of substrate metabolism outside of a hospital-based research unit.