The effect of the electrical charge on the intestinal absorption of a protein was studied in normal adult rats. Chicken egg lysozyme (Lyz), a basic protein with a molecular weight of 14,300, was selected and several techniques for chemical modification were applied. Then, the intestinal absorption of Lyz derivatives was evaluated by measuring the radioactivity in plasma and tissues, following administration of a ¹¹¹In-labeled derivative to an in situ closed loop of the jejunum. After the administration of ¹¹¹In-Lyz, the level of radioactivity in plasma was comparable with the lytic activity of Lyz, supporting that the radioactivity represents intact Lyz. ¹¹¹In-cationized Lyz showed a 2-3 times higher level of radioactivity in plasma, while the radioactivity of ¹¹¹In-anionized Lyz was much lower. The absorption rate of ¹¹¹In-Lyz derivatives calculated by a deconvolution method was correlated for the strength of their positive net charge. A similar relationship was observed using superoxide dismutase. These findings indicate that the intestinal absorption of a protein is, at least partially, determined by its electrical charge.