Serum levels of soluble IL-2R (sIL-2R) were measured in blood donors seropositive for HIV. Approximately one-half (53/101) of these seropositive donors exhibited increased serum sIL-2R levels compared with seronegative controls (n = 65). Further, a significant inverse correlation was observed between serum sIL-2R levels and CD4 cell levels in seropositive study participants. These findings suggest that increased serum sIL-2R levels in HIV infection may be linked to CD4 cell loss, and thus reflective of the stage of HIV-induced disease.