The ingestion of food antigens usually results in the induction of oral tolerance, but the clinical and immunologic consequences of brief exposure to cow's milk proteins during the neonatal period are not well-documented. The aim of this work was to study immunoglobulin (Ig)E and IgG responses to cow's milk proteins and ovalbumin after exposure during the first three days of life in infants who were otherwise exclusively breast-fed. A group of 129 infants was randomly assigned at birth to one of three feeding regimens: human milk (HM), cow's milk formula (CMF), or a casein hydrolysate formula (CHF), during the first three days of life. They were then all exclusively breast-fed for a varying period of time and followed for two years. Serum IgG and IgE antibodies to cow's milk proteins and ovalbumin (OVA) were analyzed in blood samples obtained at birth, at 4 days and at 2, 4, 8, 12 and 24 months of age. The levels of IgG antibodies to beta-lactoglobulin (IgG-BLG) and bovine serum albumin (IgG-BSA) were higher in the CMF and the HM groups than in the CHF group for up to two years. This was particularly obvious for IgG-BLG in infants who started weaning before two months. The levels of IgG antibodies to casein (IgG-CAS) were higher in the CMF group, as compared with the CHF group at 8 and 12 months. The levels of IgG antibodies to OVA were similar in all three feeding groups. The levels of IgE antibodies to CAS or OVA were similar in the three feeding groups. Exposure to cow's milk during the first three days of life stimulated IgG antibody production to cow's milk proteins and this was still obvious at 2 years of age, while feeding with a casein hydrolysate during the first three days of life was associated with low levels of IgG antibodies to cow's milk proteins.