In asymptomatic patients infected by HIV-1, the level of IL-10, a cytokine with immunosuppressive activity, is associated with the course of HIV infection towards AIDS. We show that HIV-1 Tat, a viral protein secreted by infected cells, induces IL-10 production by human peripheral blood monocytes. The analysis of the signal transduction pathways strongly suggests that the protein kinase C may play an essential role in this induction. Stimulation by Tat induces nuclear translocation of the transcription factor NFkB the activation of which seems to be necessary for IL-10 production. Using microspectrofluorimetry and confocal microscopy, we also show that Tat induces a calcium influx.