The anaphylatoxin C3a is an important inflammatory mediator in the innate and adaptive immune systems. Recent reports in various animal models have fostered the role of C3a in mediating allergic reactions such as pulmonary allergies. However, data in humans are limited and the cellular targets for C3a are not fully understood. We sought to explore human dendritic cells as a new target for C3a, because C3a receptor (C3aR) expression has been described on myeloid cells, and dendritic cells are likely make contact with C3a at sites of inflammatory reactions. In this study, we demonstrated the expression of the C3aR on human monocyte-derived dendritic cells (MoDC) and its up-regulation by interferon (IFN)-α, IFN-γ and prostaglandin E2 (PGE2). The strongest up-regulation was yielded by the combination of IFN-α+ IFN-γ. Tumour necrosis factor-α (TNF-α) down-regulated the C3aR. After up-regulation of the C3aR by IFN-α+ IFN-γ, C3a significantly up-regulated the surface expression of CD54, CD83 and CD86, but not of CD40, CD80 or human leucocyte antigen (HLA)-DR. C3a had no effect on the production of interleukin (IL)-10 or IL-12p70, or on the capacity of MoDC to stimulate autologous T-cell proliferation. However, C3a had a direct migratory effect on MoDC, as indicated by the induction of F-actin polymerization and migration in Boyden chamber experiments, which was pronounced after up-regulation of the C3aR with IFN-α+ IFN-γ. Therefore, dendritic cells represent another group of target cells that might be recruited by C3a to areas of inflammation, in particular under conditions where IFNs are increased in the surrounding environment.