Enzymatic in vitro hydrolysis was evaluated as a possible treatment to abolish the allergenicity of whey proteins in view of their use in infant formulas. Guinea pigs without prior immunological contact (including fetal life) with cow's milk were fed various preparations of cow's milk proteins. Oral exposure to milk or untreated whey protein led to anaphylactic sensitization of the animals. In contrast, trypsin-hydrolyzed whey protein and a peptide preparation produced from the tryptic hydrolysate by ultrafiltration were devoid of sensitizing capacity by the oral route. The hydrolysate (crude or purified) was also ineffective in triggering local or systemic anaphylaxis in previously sensitized animals.