The effect of surface modification of indium tin oxide (ITO) electrode on its potential response to tryptophan was investigated for ITO substrates with different surface roughness. It was found that a small difference in surface roughness, between similar to 1 and similar to 2 nm of R-a evaluated by atomic force microscopy, affects the rest potential of ITO electrode in the electrolyte. A slight difference in In:Sn ratio at the near surface of the ITO substrates, measured by angle-resolved X-ray photoelectron spectrometry and Auger electron spectroscopy is remarkable, and considered to relate with surface roughness. Interestingly, successive modification of the ITO surface with aminopropylsilane and disuccinimidyl suberate, of which essentiality to the potential response to indole compounds we previously reported, improved the stability of the rest potential and enabled the electrodes to respond to tryptophan in case of specimens with R-a values ranging between similar to 2 and similar to 3 nm but not for those with R-a of similar to 1 nm. It was suggested that there are optimum values of effective work function of ITO for specific potential response to tryptophan, which can be obtained by the successive modification of ITO surface. (C) 2011 Elsevier Ltd. All rights reserved.