We have previously reported that the measles virus (MV) could productively infect human dendritic cells (DC), derived in vitro from CD34+ cord blood progenitors in the presence of GM-CSF and TNF-alpha. In this study, we provide evidence that freshly isolated Langerhans cells (LC), which are immature dendritic cells located in skin and mucosal epithelia, are susceptible to MV infection in vitro as assessed by viral antigen expression by both LC syncytia and LC remaining as single cells. Moreover, MV-infected LC completely block naive allogeneic CD4+ T cell proliferation in response to uninfected LC. This active inhibitory effect is not due to virus transmission from infected LC, is independent of the maturation stage of LC at the time of infection and is antigen non-specific and MHC-unrestricted. Thus, both immature and mature LC are susceptible to measles virus infection, which turns these efficient antigen-presenting cells into active tolerogenic cells. LC infection may explain the long lasting immune suppression observed during natural measles infection.