The aim of this study was to assess the antibody reactivity in HIV-infected subjects against an HIV-1 p24 sequence, p226 (aa226-237), including a seven amino acid epitope showing immunosuppressive activity in vitro and to evaluate the relationship between anti-peptide antibody levels and disease progression. Sera of HIV-infected subjects, at different stages of disease, were compared to control sera in a retrospective evaluation. Recombinant HIV-1 p24 and p24- and control-peptides were used in an enzyme immunoassay as targets for antibodies present in the sera. Antibodies directed against the whole p24 protein and its peptides were found in all the sera studied but at different levels. The anti-p226 reactivity was not significantly different at different clinical stages. Nevertheless, it was inversely correlated to the reactivity directed against the whole protein, that was lower in subjects characterized by low CD4 cell numbers.