Cow's milk allergy is quite frequent in the first years of human life. When breast-feeding is not possible, a cow's milk substitute must be provided for allergic subjects. Different alternatives to cow's milk have been suggested as protein sources (soy, hydrolyzed proteins, goat's milk, etc.), but all these dietetic solutions are not without risks for polyallergic or more sensitive subjects. To obtain new information on the suitability of other mammalian milks for allergic children, we evaluated the cross-reactivity between milk proteins from cow and buffalo. The cross-reactivity of cow whey proteins with IgG and IgE anti buffalo whey proteins and cross-reactivity of cow caseins with IgG and IgE anti buffalo caseins, obtained by immunization of Swiss albino mice, was carried out by ELISA. IgEs and IgGs from mice allergic to cow's milk are capable of cross-reacting with buffalo milk proteins. Homologies in amino acidic composition could justify the cross-reactivity observed between caseins and whey proteins from cow's and buffalo's milk.