BACKGROUND Because sensitization to cow's milk is a common finding in children, the identification of safe alternative protein sources is important in the management of childhood allergy. OBJECTIVE To evaluate, in an animal model, the allergenicity of a novel formula based on hydrolyzed rice proteins. METHODS We conducted an experiment involving 130 guinea pigs, from 7 to 12 days old at the onset of the study. The animals were divided into 13 groups and were given, ad libitum, one of the following liquids to drink: (1) rice hydrolysate formula (RF), (2) a conventional cow's milk formula (CMF), or (3) water. After a 37-day sensitization period, a challenge was given, consisting of an intravenous injection of either isolated proteins or ultracentrifuged formulas (uCMF and uRF). Specific IgG antibodies to beta-lactoglobulin, casein, and whole rice protein were measured by enzyme-linked immunosorbent assay. RESULTS When animals fed CMF were challenged with beta-lactoglobulin, casein, or whole uCMF, they showed significantly more reactions than did those fed RF when challenged with the same proteins (P < 0.001). In the groups fed RF, no reaction was observed after challenge with uRF, and only 2 mild reactions occurred after challenge with rice protein. Very low levels of specific IgG antibodies to rice protein were noted in all the groups, including the RF-fed animals, and no significant differences were evident between groups. CONCLUSIONS The findings suggest that this new formula based on hydrolyzed rice proteins has a very low sensitizing capability.