IL-21 is a relatively newly discovered multifunctional and pleiotropic cytokine. It is produced primarily by CD4(+) T cells, the principal targets of the virus, and therefore this cytokine has special relevance to HIV infection. Here we show for the first time that serum levels of this cytokine are significantly reduced in HIV-infected AIDS patients and correlate significantly with their CD4(+) T-cell counts. These data suggest that the cytokine levels could act as a valuable biomarker for the progression of AIDS.