We compared the prevalence of HIV p24 antigenemia in black and white US patients with HIV infection. The prevalence of HIV antigenemia increased with severity of HIV disease (P less than 0.001). In all clinical categories, whites were more likely to be HIV-antigenemic than blacks (overall prevalence 38 versus 18%; P less than 0.01). Anti-p24 antibodies were detected in a higher proportion of blacks (84%) than whites (65%; P = 0.02). Blacks had significantly higher total serum immunoglobulin levels than whites (median 3.8 versus 3.2 mg/dl; P less than 0.00001). Racial differences in HIV antigen expression may result from differences in humoral response to HIV infection. These differences should be considered when HIV antigen is used as a surrogate marker in clinical trials.