Control of pandemic human immunodeficiency virus type 1 (HIV-1) infection ideally requires specific mucosal immunity to protect the genital regions through which transmission more often occurs. Thus a vaccine that stimulates a disseminated mucosal and systemic protective immune response would be extremely useful. Here we have investigated the ability of a chimeric plant virus, cowpea mosaic virus (CPMV), expressing a 22 amino acid peptide (residues 731-752) of the transmembrane gp41 protein of HIV-1 IIIB (CPMV-HIV/1), to stimulate HIV-1-specific and CPMV-specific mucosal and serum antibody following intranasal or oral immunization together with the widely used mucosal adjuvant, cholera toxin. CPMV-HIV/1 has been shown previously to stimulate HIV-1-specific serum antibody in mice by parenteral immunization. All mice immunized intranasally with two doses of 10 microg of CPMV-HIV/1 produced both HIV-1-specific IgA in faeces as well as higher levels of specific, predominantly IgG2a, serum antibody. Thus there was a predominantly T helper 1 cell response. All mice also responded strongly to CPMV epitopes. Oral immunization of the chimeric cowpea mosaic virus was less effective, even at doses of 500 microg or greater, and stimulated HIV-1-specific serum antibody in only a minority of mice, and no faecal HIV-1 specific IgA.