Six stomatitis papulosa and three Orf virus strains were compared by serology and by DNA restriction analysis. A neutralization kinetic study revealed extensive serological cross-reactivity between all strains, but did not allow their classification. Restriction analysis of viral DNAs revealed two distinct groups among the stomatitis papulosa strains while the Orf virus strains formed a third, more heterogeneous group. The large heterogeneity of restriction patterns of parapoxvirus DNAs as compared to those orthopoxviruses is discussed.