In the literature there are several reports dealing with the possibility of a desensitising treatment in food allergy, but there are very few studies about the immunological mechanisms of oral desensitisation. We studied the immunological modifications in four children who underwent oral desensitisation with cow milk. Four children with cow milk allergy underwent oral desensitisation according to a standardized protocol. Total IgE, eosinophilic cationic protein in serum, and specific IgE and IgG4 to α-lactalbumin, to β-lactoglobulin and to casein were determined at the beginning of the treatment and after 6, 12 and 18 months in the 4 children treated. All the 4 treated patients successfully completed the treatment. Specific IgE to casein showed a significant reduction (p<0.01), while specific IgG4 to α-lactalbumin (p<0.02), to β-lactoglobulin (p<0.01) and to casein (p<0.01) showed a significant increase. Total IgE, eosinophilic cationic protein, and specific IgE to α-lactalbumin and to β-lactoglobulin did not show any significant modification. Control patients did not show any immunological modification and still had a positive double-blind, placebo-controlled food challenge. These results make us think that oral desensitisation in food allergy happens with the same mechanisms of traditional desensitising treatments for respiratory and insect sting allergies.