CD45 is a leukocyte tyrosine phosphatase, essential for normal immune responses. We have studied the function of splenic dendritic cells of CD45(+/+), CD45(-/-), CD45RABC and CD45RO transgenic mice. We show that there are increased numbers of plasmacytoid dendritic cells in CD45(-/-) mice. DC of all mice are capable of responding to lymphocytic choriomeningitis virus (LCMV) infection by up-regulation of MHC and costimulatory molecules. DC of CD45(-/-) mice have an impaired capacity to produce type I interferons in response to LCMV infection in vivo. These data indicate that lack of CD45 expression in DC has a profound effect on their function. This is largely restored by CD45RABC or CD45RO transgenes.