Mucous membranes are the main route of transmission of human immunodeficiency virus (HIV). Interestingly, some viral inhibitory activities have been found in saliva. The purpose of this study was to determine the level of salivary immunoglobulin A (IgA) antibodies to gp41 in HIV+ patients at various disease stages to identify whether gp41 was able to induce vigorous humoral responses. Unstimulated saliva samples were obtained from three groups of subjects (n=37): group A (HIV-), group B (HIV+, CD4+ <200/mm3), and group C (HIV+, CD4+ >200/mm3). IgA antibody levels to purified gp41 were determined by enzyme-linked immunosorbent assay (ELISA). Western blot analyses were performed using HIV+ saliva to confirm IgA reactivity to gp41. ELISA demonstrated that HIV+ subjects had higher IgA antibody to gp41 than HIV- individuals. No significant differences were noted between HIV+, CD4+ <200/mm3 and CD4+ >200/mm3 subjects. High (81.25%) IgA reactivity to gp41 was demonstrated by Western blotting of saliva from all HIV+ individuals. In conclusion, gp41 responses are important in the HIV disease process, as indicated by the high IgA levels and gp41 reactivity in saliva of HIV+ patients.