In this study we investigated the HLA association with cow milk allergy. Thirty-seven Italian children with cow milk allergy and 35 randomly selected age-matched healthy children as control group were included in the study. DNA typing was performed by restriction fragment length polymorphism (RFLP) technique. We show the first statistically significant positive association between the expression of the HLA-DQ7 antigen and cow milk allergy. Several immunological tests (skin prick test, RIA, radioallergosorbent test (RAST) and ELISA) were performed to evaluate the humoral immune responses of DQ7 positive and DQ7 negative allergic patients. Our results show that among the DQ7 positive patients the majority presented a high humoral response. Furthermore, the in vitro proliferative response of patients to the beta-lactoglobulin antigen was performed to evaluate their cell-mediated immune response. We observed that the number of the nonresponders was higher in the DQ7 positive patients when compared to the DQ7 negative patients. Our data indicate an association of HLA-DQ7 antigen with cow milk protein allergy and that the DQ7 positive patients had a prevalence of humoral rather than cellular responses.