Infant formulae based on hydrolyzed proteins or elemental diets offer the best treatment of cow's milk allergy whenever exclusive breast-feeding is not possible. In situations with a family history of atopy, formulae using other protein sources such as soya or chicken meat can also be a good preventive measure. The food industry needs reliable research methods for the evaluation of every new option before considering clinical trials. Allergenicity of cow's milk proteins was evaluated by the induction of mouse monoclonal reagins and also by oral administration of milk preparations to mice and guinea pigs. Animals initially raised on commercial diets containing about 1% milk whey could not be sensitized. Maintenance of a milk-free diet from pregnancy until weaning, and feeding milk in a liquid form led to an optimal sensitization of the guinea pigs. These animals suffered systemic anaphylaxis and their sera sensitized skin in virgin hosts. Under optimal conditions, while giving liquid preparations to drink, a considerable proliferation of the milk flora occurred. As no mucosal alterations could be detected, primary gut damage due to infection was probably not the triggering factor for oral sensitization. Bacterial products (e.g., endotoxins, enterotoxins) could stimulate the gut response towards milk proteins, either due to an adjuvant effect or to increased mucosal permeability. Microbial contamination of milk is practically unavoidable and it can generally induce biologic activity, e.g., fresh milk regularly gives a positive limulus test for endotoxin by the time it is consumed or processed. Reduction of bacterial contaminants by milk protective factors might help to prevent oral sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)