A high percent of annual neonatal mortality attributed to orf infection was observed between 2001 and 2004 in 2 sheep and 2 mixed (sheep and goat) flocks of Northern Greece. In order to protect the neonatal lambs and kids from orf infection a commercially available live orf vaccine was used. Pregnant sheep and goats were vaccinated subcutaneously a month before parturition, while 10 sheep and 10 goats in each flock remained unvaccinated and were used as negative controls. The vaccine was significantly effective (P<0.05) in reducing the orf lesions and the mortality rate in lambs and kids of the 4 flocks. During the next year 3 of the 4 flocks were revaccinated. A significantly low percentage of orf lesions and neonatal mortality continued to occur in revaccinated flocks, while a significant percentage (P<0.05) of orf lesions and neonatal mortality reappeared in the nonrevaccinated flock. The antibody titres in vaccinated sheep and goats were increased significantly on days 60 and 105 post-vaccination, while the titres in the controls remained low (P<0.05).