During the last few years infrared spectrometry has been investigated as a non-invasive clinical tool for improved understanding of in-vivo processes. Oral mucosa has been suggested as an especially suited subject for drug delivery and in vivo monitoring of endogenous body metabolites due to histological and physicochemical reasons. The attenuated total reflection (ATR) technique was used to characterize the outmost epidermal layer of human oral mucosa by means of Fourier-transform infrared spectroscopy. The penetration depth of the probing radiation in the mid-infrared fingerprint region, using a ZnSe-crystal for the horizontal ATR accessory, is in the order of a few micrometers so that microlayer information can be obtained by such a technique. Spectra of outer human lip and saliva components are presented for comparison. For several test persons, lip spectra were recorded during oral glucose tolerance tests. The individually varying blood glucose concentration was followed by means of frequent blood testing. Variability of the outmost microlayer has been studied using factor analysis of the ATR inner-lip spectra. There is no clear evidence that blood glucose concentration can be followed by ATR-spectroscopy of oral mucosa. Non-invasive spectroscopic methods exploiting trace signals require special attention paid to the variability due to person-to-person differences and changes in physiological conditions.