The influence of sesamol, an antioxidant in processed sesame oil, on oxidative modification of human erythrocyte membrane proteins was investigated. Human erythrocytes were incubated with sesamol at various concentrations up to 10 mM at 37 degrees C for 1 h. The amounts of hemoglobin bound to the membranes and detergent C12E8-insoluble membrane protein aggregates were increased as the concentration of sesamol increased. Western blot analysis indicated that aggregates of band 3 protein were increased by the treatment. Binding of anti-band 3 antibody to the erythrocytes was increased by the treatment. Isolated cell membranes were incubated with sesamol similarly. Aggregates of band 3 protein were also increased, indicating that the band 3 protein aggregation was little affected by hemoglobin bound to the membranes. Aggregation of band 3 protein in the treatment of isolated cell membranes was partially prevented when the treatment was conducted under anaerobic conditions, suggesting that augmentation of the protein aggregation by sesamol involved both oxygen-dependent and oxygen-independent pathways. Among phenolics, sesamol showed a distinctive feature to increase band 3 protein aggregation in erythrocyte membranes and to enhance anti-band 3 binding to erythrocytes.