The concept of combining several genes in order to immunize against a microbial agent has been tested. We selected human immunodeficiency virus (HIV) genes that individually have been shown to mediate immune responses against HIV proteins. These proteins were the regulating genes/proteins of HIV-1 rev, tat and nef as well as structural genes for gp160 under the control of rev, and the capsid p24 represented by the larger precursor gene p37. Two findings were of particular interest. The combination of these five gene constructs gave strong reactivity to all of them, compared with previous results using each one in single injections. The intranasal immunization route gave good mucosal reactivity by inducing IgG, IgA and T-cell proliferative responses.