The CD8-expressing dendritic cells (DC) present in mouse spleen have been shown to have a regulatory effect on the CD4 and CD8 T cells they activate, restricting subsequent T cell proliferation by either inducing apoptotic T cell death (CD4 T cells) or by limiting endogenous cytokine production (CD8 T cells), To determine the role of the CD8 molecule itself in these regulatory phenomena, the DC from CD8 null mice were studied, The DC marker DEC-205 (NLDC 145) was used as a surrogate marker for CD8, since the expression of these two molecules on splenic DC was closely correlated. DC levels were normal, and the incidence of DEC-205(+) and DEC-205(-) DC was normal in CD8 null mice, indicating that the absence of CD8 did not affect DC development, The proliferative response of T cells to allogeneic DEC-205(+) DC from either CDS-/- or CD8(+/+) mice was similar and was much less than the response to DEC-205(-) DC from these mice, This applied to both the CD4 and the CD8 T cell responses. Thus the lack of the CD8 molecule did not affect the stimulatory or regulatory properties of the DC, The regulatory CD8(+) DEC-205(+) DC therefore differ in that respect from antigen-presenting 'veto' cells, where CD8 itself is involved in transmitting negative signals to the T cells. DEC-205 may prove to be a more pertinent marker of the regulatory DC population.