BACKGROUND AND OBJECTIVES: Sheeppox virus causes systemic disease in sheep that is often associated with high morbidity and mortality. Protection against sheep pox is mainly based on medical prophylaxis, vaccination being the only way. In Morocco, and up to now, there is no available information about local challenge strain to use for controlling the efficiency of vaccines produced against sheep pox. Hence, the objective of the present study was to evaluate and compare the pathogenicity of seven Sheeppox virus (SPVs) isolates from 1993-1995 in Morocco. MATERIALS AND METHODS: These seven SPV isolates have undergone various tests to evaluate their pathogenicity: Passages and titration on cell culture, Experimental inoculation on sheep, Virus-neutralization, In vivo titration and viral re-isolation by real-time PCR assay. RESULTS: All infected lambs showed severe clinical signs, while most of them have been reproduced on 5 dpi and persisted until 21 dpi. The lambs infected by Oj1P4, Oj2P4 and BerP5 appeared lethargic, reluctant to move compared to those infected by other isolates. The results also revealed that all isolates were able to induce serological response. Virus isolation from infected organs and blood and amplification of the viral DNA by real-time PCR proved the presence of the virus in tissues and blood of infected lambs. These Moroccan SPVs demonstrated that the three isolates Oj1P4, Oj2P4 and BerP5 have a high pathogenicity; especially the BerP5 isolate which has an important infectious titer. CONCLUSION: These results demonstrate that the Berkane isolate is the most pathogenic of the tested isolates and it can be an excellent challenge strain for the control of the efficiency of vaccines against sheep pox produced in Morocco.