An organically modified sol-gel glass (ORMOSIL) encapsulating pyrroloquinoline quinone (PQQ)-modified electrode for the rapid, sensitive and simple determination of thiol-containing compounds such as cysteine and glutathione is reported. The effect of applied potential, nature of thiol compound and pH on the response of the sensor was examined and optimum conditions were determined. The electrochemical responses and detection limits were found to be sensitive to the nature of thiols and pH. The electrochemical responses for cysteine and glutathione at an applied potential of À 0.2 V (vs. Ag/AgCl) were found to be linear with detection limits of 18 nM for cysteine and 36 nM for glutathione at pH 3.5, whereas the detection limits at pH 8.5 were 0.5 mM for cysteine and 1 mM for glutathione. The electrode retained 95% of the original response for 7 days when stored at 4 8C. The ORMOSILencapsulated PQQ was also characterized by spectrophotometry. The absorbance measurement using 5,5'-dithiobis-(2-nitrobenzoic acid) at 412 nm justify the PQQ-mediated oxidation of glutathione whereas fluorescence measurements (excitation wavelength ¼ 380 nm; emission wavelength ¼ 480 nm) justify the successful encapsulation of PQQ in ORMOSIL matrix.