Citation Mestecky J, Alexander RC, Wei Q, Moldoveanu Z. Methods for evaluation of humoral immune responses in human genital tract secretions. Am J Reprod Immunol 2011; 65: 361-367 The compilation of epidemiological, virological, and immunological data clearly indicates that HIV-1 infection must be considered primarily as a disease of the mucosal immune system. The earliest and most dramatic alterations of the immune system occur in the mucosal compartment. However, the mucosal immune systems of the genital and intestinal tracts display remarkable immunological differences that must be considered in the evaluation of humoral immune responses in HIV-1-infected individuals or in volunteers immunized with experimental HIV vaccines. In this regard, marked differences in the dominant Ig isotypes, molecular forms of HIV-1-specific antibodies, and their distinct effector functions in the genital versus intestinal tracts must be carefully evaluated and considered in the measurement and interpretation of humoral immune responses. Appropriate controls and alternative immunochemical assays should be used to complement and confirm results generated by ELISA, which are prone to false positivity. Special precautions and rigorous controls must be used in the evaluation of antibody-mediated virus neutralization in external secretions of the genital and intestinal tracts. © 2010 John Wiley & Sons A/S.