Interference by membrane permeable substances on nonspecific electrodes is a major problem in glucose sensing. Alanine, lysine, phenylalanine, and cystine were chosen for study to gain insight into this problem. These compounds represent the classes of mono-amino aliphatic, di-amino aliphatic, aromatic, and sulfur containing amino acids, respectively. Cyclic voltammetry experiments were performed using a Pt electrode (1.77 mm2). The reductive current of glucose at -0.750 V versus Ag/AgCl was measured with increasing concentrations of interfering substances in Krebs-Ringer phosphate buffer (pH 7.4) at 37 degrees C. Experimental results have shown that these amino acids have an inhibitory effect on the glucose signal. An important finding was that the interferences from phenylalanine and cystine were more pronounced than those of lysine and alanine. An initial drop in the glucose signal was seen at less than 2.0 mg/dl of alanine or lysine and at less than 0.5 mg/dl of phenylalanine or cystine. Additional increase in the concentrations of interfering substance did not cause further appreciable signal reduction. The results confirm that glucose sensing using a non-specific electrode is possible in fluids containing interfering substances such as amino acids.