Although measurement of capillary blood glucose remains the standard method of self-monitoring for persons with diabetes mellitus, a less-invasive method of monitoring would be desirable. Measurement of dermal interstitial fluid glucose might meet this need. To test this possibility, plasma glucose, capillary blood glucose (current standard), and dermal interstitial fluid glucose were measured in 17 subjects with type I diabetes during a 5-hour pre- and postprandial period when plasma glucose was changing rapidly. The objective was to assess the ability of dermal interstitial fluid glucose to accurately predict plasma glucose over a wide range of potential glucose concentrations. Dermal interstitial fluid glucose was highly correlated with plasma glucose (r = 0.95, p < 0.0001). The mean absolute and percent differences between dermal interstitial fluid glucose and plasma glucose were 1.2 mmol/L (21 mg/dl) and 10.6%, respectively. The kinetics of dermal interstitial fluid glucose and plasma glucose were similar. There was no significant difference between dermal interstitial fluid glucose and plasma glucose in mean glucose excursion, peak glucose concentration, or time to peak glucose concentration. The correlation between dermal interstitial fluid glucose and plasma glucose was as strong as the correlation between capillary blood glucose and plasma glucose. In conclusion, dermal interstitial fluid glucose can be used to estimate plasma glucose, and has the potential to be used for monitoring patients with diabetes mellitus