Non-invasive blood glucose measurement through the mucous membrane of the lip was investigated using Fourier transform infrared (FT-IR) spectroscopy with an attenuated total reflection (ATR) prism. To achieve easy attachment and easy control of attachment pressure of the ATR prism to the mucous membrane of the lip, a chalcogenide optical fiber with an ATR prism built in the tip was used. The same glucose-specific peaks at wave numbers of 1080 and 1033 cm-1 as glucose solutions were found in a spectrum through the mucous membrane of the lip. With a constant pressure of the ATR prism to the mucous membrane of the lip of 6.7 x 10(3) dyn/cm2, coefficients of variation of measurements within the day and of day-to-day measurements were 3.8 and 5.4% respectively. To eliminate baseline drifts and interference of body constituents other than glucose, the difference absorbances at 1080 cm-1 between spectra measured at the postprandial state and background spectrum obtained at the fasting state as an individual characteristic were evaluated. Following i.v. pulsatile injection of glucose, the difference absorbances at 1080 cm-1 nicely followed the changes in blood glucose concentrations with a time delay of 4 min. In daily blood glucose monitoring, a highly significant correlation between the difference absorbances and increases in blood glucose concentrations above the fasting level was obtained (r = 0.920, P < 0.01). From these experiments, it was suggested that FT-IR spectroscopy with a chalcogenide optical fiber could be useful clinically for non-invasive monitoring of glucose through the mucous membrane of the lip.