This study was designed to distinguish between antibodies in HIV-1-infected patients directed against epitopes accessible on the native HIV-1 envelope (Env) complex and non-native Env epitopes. Peptide p#13 (Env. aa642-673) containing the neutralising 2F5 epitope and recombinant soluble glycoprotein 160 (rsgp160) were used in ELISA to determine the antibody (Ab) reactivity in sera of 116 HIV-1-infected individuals and 18 HIV negative controls. The reactivity of sera classified CDC stage C against p#13 was significantly decreased in comparison to stage A sera, while staying constant against rsgp160. Accordingly, in 6 out of 8 individual patients tested over time the response against p#13 was declining at later time points of infection. The reactivity of patients' sera against p#13 corresponded directly to the recognition of infected T cells and largely also to the CD4 cell count. The causal relationships of these phenomena are not clear. It is conceivable that antibodies against epitopes on HIV are lost or escape mutants arise and consequently control of HIV is lost and virus load increases as it is known for CDC stage C. Alternatively, increasing virus load may affect B cells recognising native Env epitopes and turn antibody production down by some mechanism. In this latter scenario helper T cells might have a critical role.