The allergenicity and antigenicity of cow milk proteins are age dependent. Because the nonspecific and specific factors inhibiting the passage of cow milk proteins through the epithelial layer of the intestine are deficient at birth, although developing during early infancy, allergy to cow milk may be acquired during the first year of life. Allergic reactivity to cow milk is lost during childhood in the vast majority of cases. This change may depend at least partly on the development of the local immune system of the gut producing antigen-specific IgA antibodies. Circulating IgG antibodies to cow milk proteins are always produced when an infant has cow milk in the diet but are not associated with allergy; their titer is reduced with age. Clinical challenge tests show that most cow milk-allergic patients react to several protein fractions of cow milk. A patient may have IgE antibodies to several fractions of cow milk, measured either by skin testing or by radioallergosorbent test. Likewise, various tests for cell-mediated immunity may show positive reactions to several fractions. No single major allergen is apparent in cow milk, according to either the challenge tests or laboratory procedures: casein, alpha-lactalbumin, and beta-lactoglobulin all show a high proportion of positive reactions.