It has been shown in an animal model that cow's milk (CM) protein hydrolysates do not elicit an antibody response to CM proteins and do not induce passive cutaneous anaphylaxis. In addition, babies fed with these formulae during the first months of life do not show antibodies to betalactoglobulin (BLG). These data suggest that these hydrolysates are not antigenic, therefore they have been employed as CM substitutes for the management of infants with CM allergy (CMA). We report five exclusively breast fed infants aged 3 to 8 months (median age = 5 mo) with IgE-mediated CMA, who experienced allergic reactions when they were first fed (median age = 5 months) with a small amount of CM whey protein hydrolysate (Alfa-Ré, Nestlé). Family history was positive for atopy in 3/5 babies. All infants had atopic dermatitis during breastfeeding, positive skin tests, and RAST to CM proteins as well as to Alfa-Ré. Total IgE levels ranged from 45 to 2,990 U/mL. These data show that Alfa-Ré, a CM whey protein trypsin hydrolysate, can trigger severe allergic reactions in children with CMA and it should be employed with great caution as a CM substitute in the management of CMA.