The association between viral activity and antibody profiles was investigated in 202 individuals infected by the human immunodeficiency virus (HIV) grouped according to their Walter Reed clinical stage. Each study group was subdivided into subjects positive or negative for markers of active viral replication: presence of serum p24 antigen and viral culture. In Western blots using recombinant antigens, sera of HIV-positive individuals with positive viral markers had a significantly lower antibody reactivity to several viral proteins than did individuals without viral markers. Noticeably, proteins of the gag (p24, p17) and env (gp120, COOH-terminal part of gp41) open-reading frames revealed a decreased reactivity. The antibody response to the regulatory proteins revealed no or poor association with viral activity in the host. The results suggest that seroreactivity is mainly influenced by factors reflecting the viral activity of an HIV-infected individual, while the clinical stage of the patient is less important. Especially, reductions in antibodies against gp120 and p17 were useful markers associated with increased viral activity.