To investigate the relation between human immunodeficiency virus (HIV) antigenemia and clinical manifestations of HIV infections, we studied 96 patients with hemophilia who were positive for HIV antibody, for a median of 34 months. Every 4 to 10 months a clinical and laboratory examination was performed and serum samples were tested for three HIV markers: HIV antigen, antibody to p24, and antibody to gp41. Twenty-two subjects (23 percent) were found to be positive for HIV antigen: 8 were positive upon entry and remained so (Group 1), and 14 became positive during the study, 4 to 26 months after HIV antibody appeared (seroconversion), 13 of whom remained positive for HIV antigen (Group 2). Most subjects positive for HIV antigen had low or undetectable titers of antibody to p24, whereas the antibody titer to gp41 remained high. In Group 2, patients with low p24 antibody titers had further decreases in their titers before or at the time HIV antigen appeared. Once present, HIV antigen persisted and tended to increase in concentration. In contrast to Group 3 (negative for HIV antigen, low anti-p24 titer) and 4 (negative for HIV antigen, high anti-p24 titer), the groups positive for HIV antigen had significantly higher incidences of acquired immunodeficiency syndrome (P = 0.05), immunodeficiency-related infections (P less than 0.001), and immune thrombocytopenia (P = 0.001), and had more severe disease as measured by the Walter Reed staging system (P less than 0.001). In this study, HIV antigen appeared to be a better predictive marker of HIV-related complications than the absolute T4+ count. These results suggest that HIV antigenemia indicates a poor clinical prognosis.