BACKGROUND The first exposure to food antigens provokes an immune reaction in an infant, its type depending on the quantity and frequency of doses and the age at introduction, and also being influenced by genetic factors. Most infants develop tolerance to food antigens, but in a small minority they provoke adverse symptoms. OBJECTIVE To study the effects of breast and formula feeding and other environmental and genetic factors on the subsequent type of cow's milk allergy classified by the presence or absence of immunoglobulin (Ig) E antibodies to cow's milk. METHODS A cohort of 6209 infants was followed prospectively from birth for symptoms of cow's milk allergy. The infant-feeding regimen was recorded at the maternity hospital and at home. At a mean age of 6.7 months, a total of 118 infants (1.9%) reacted adversely to a challenge with cow's milk. Before the challenge, the response to a skin-prick test with cow's milk and serum IgE cow's milk antibodies was measured. RESULTS At challenge, 75 (64%) infants showed IgE-positive reactions to cow's milk, their most common symptom being acute-onset urticaria. Significant risk factors for the presence of IgE cow's milk antibodies in allergic infants were long breast-feeding (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.6-9.8), exposure to cow's milk at the maternity hospital (OR 3.5, 95% CI 1.2-10.1) and breast-feeding during the first 2 months at home either exclusively (OR 5.1, 95% CI 1.6-16.4) or combined with infrequent exposure to small amounts of cow's milk (OR 5.7, 95% CI 1.5-21.6). Fifty infants had their first adverse symptoms during exclusive breast-feeding, and 32 infants were sensitized during exclusive breast-feeding. Most of the infants in both cases were IgE-positive: 37 and 23, respectively. CONCLUSIONS In infants who are prone to developing cow's milk allergy, prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of cow's milk during the first 2 months of life induces development of IgE-mediated response to cow's milk.