Aqueous chlorine reacts with tyrosine to form ring-chlorinated products. Ring substitution occurs at Cl:tyrosine mole ratios greater than 1. Because the nitrogen function of amides is much less reactive than that of amines, the aromatic ring of N-acetyltyrosine is chlorinated at chlorine:substrate mole ratios less than 1. When an aqueous solution of the gastric protein pepsin was chlorinated (37 degrees C, 45 min), tyrosine residues were chlorinated at pH 2 but not at pH 8. The carbohydrate, protein, and chloride concentrations in stomach fluid from fasted rats were determined. When varying concentrations of aqueous chlorine (20-180 mg/L Cl2) were added to the stomach fluid at pH 2, tyrosine residues were mono- and dichlorinated on the aromatic ring. The amount of mono- to dichlorination products varied with the concentration of aqueous chlorine. A mechanism is proposed. The implications for toxicological studies involving chlorinated drinking water are discussed.