The binding ability of bovine milk caseins with mutagenic heterocyclic amines was investigated. Binding was determined with 2 mg of casein and 20 micrograms of heterocyclic amine in .40 ml of pH 7.4, 50 mM phosphate buffer, at 37 degrees C, in a shaker for 10 min. The unbound heterocyclic amine in protein-free ultrafiltrate was analyzed by HPLC. The binding ability of whole casein, alpha s-casein, beta-casein, and kappa-casein, respectively, was 90.08, 83.06, 90.92, and 96.70% with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole; 85.48, 51.54, 63.62, and 82.71% with 3-amino-1-methyl-5H-pyrido[4,3-b]indole; and 87.03, 59.77, 97.04, and 88.30% with 2-amino-6-methyldipyrido[1,2-a:3',2'-d]-imidazole. Higher binding of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole to alpha s-casein, beta-casein, and kappa-casein was observed at pH above 7.4, and the binding was inhibited at pH below 6.5. The maximum binding of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole to these caseins was at pH 6.6 and 7.4. The binding was inhibited at alkaline pH above 8.5 and acidic pH below 6.5.