Hepatitis B virus core protein (HBc) in particulate form is a potent immunogen for the design of vaccines with a broad T-cell reactivity. Hybrid HBc proteins with N-terminal insertions of human immunodeficiency virus (HIV-1) B- and T-cell epitopes from gp41 and p34 pol, respectively, were constructed HBc hybrids formed particles with HIV-1 epitopes exposed on the surface. The proliferative response of peripheral blood mononuclear cells (PBMC) from HIV-1 infected donors to the hybrids was studied in vitro and compared to that of synthetic peptides representing the same HIV-1 sequences. The epitope from p34 pol induced PBMC proliferation both when inserted into HBc and as a peptide. The epitope from gp41, when inserted into HBc, and to a lesser extent the relevant peptide caused a decreased reactivity. The inhibitory effect of the HBc hybrid carrying the gp41-epitope was pronounced even in the HIV-1 infected donors with proliferative responses to HBc. The similarity between the mode of action of the peptides and hybrid HBcs implies either correct processing of the latter or T-cell recognition of HIV-1 epitopes in the intact hybrid HBc particles.