Equine herpesvirus-1 (EHV-1) causes rhinopneumonitis, abortion and CNS disorders in horses. Using intranasal inoculation, the mouse model of this disease mimics the major pathogenic and clinical features of the equine disease. The aim of this study was to investigate whether murine dendritic cells (DC) can be infected with EHV-1 and whether they can be used as cellular vaccines for the induction of prophylactic anti-EHV-1 immunity. It was found that the DC lines FSDC, D2SC1, 18 (all H-2d) and 80/1 (H-2k), when incubated with the Ab4 strain of EHV-1, do not change their morphology and phenotype but sustain virus replication and induce proliferation of naive, syngeneic T cells. An even stronger proliferation of T cells was seen when DC were used that had been pre-exposed to heat-inactivated virus. DC lines were therefore pulsed with inactivated virus and were then administered intranasally to either BALB/c or C3H mice on days -25, -15 and -5. Control groups received either medium, unpulsed DC or inactivated virus only. Animals were challenged with EHV-1. Whereas mice of control panels showed clinical signs of EHV-1 disease and 27% died, animals immunized with the pulsed DC lines showed only subtle clinical symptoms, lost significantly less weight, exhibited a reduced virus load in their lungs and CNS and did not succumb to the disease during the observation period. These results show that murine DC can present EHV-1 and initiate a protective anti-viral immunity in vivo.