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 aminoacid peptide (residues 731-752) of the transmembrane gp41 protein of HIV-1 IIIB (CPMV-HIV/1), to stimulate HIV-l-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-l-specific serum antibody in mice by parenteral immunization. All mice immunized intranasally with two doses of 10 mu g of CPMV-HIV/1 produced both HIV-l-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 mu g or greater, and stimulated HIV-1-specific serum antibody in only a minority of mice, and no faecal HIV-I specific IgA. (C) 1998 Elsevier Science B.V. All rights reserved.