Outbreaks of contagious ecthyma (CE) have been reported in vaccinated sheep and studies were undertaken to investigate the causes of these vaccination failures. The vaccination procedure was very effective in inducing a lesion at the site of vaccination, but a proportion of sheep (17 percent) were not fully protected when reinoculated with CE virus 4 weeks later. The size of the primary vaccination lesions, virus neutralizing antibody titers and virus-specific lymphocyte stImulation indices could not be used to predict the degree of protective immunity. Measurement of the neutralizing antibody and virus-specific lymphocyte transformation responses suggested that there was a minimal systemic immune response following CE virus inoculation. Higher levels of systemic immunity may be induced by parenteral administration of live CE vaccines compared to the current procedure of inducing a localized skin infection. Replication of CE virus in buffy coat cells in vitro suggested that the virus may replicate in macrophages and therefore parenteral administration of vaccines may be feasible. Occurrence of CE in vaccinated sheep raised questions about possible variation of antigenic types of CE virus. It was found that cross-neutralization and delayed-type hypersensitivity tests could not be used to classify the CE viral isolates. However, analysis of the structural polypeptides of CE virions revealed differences among the isolates in the position of distinct polypeptide bands in the molecular weight region of 37,000-44,000 daltons, allowing the isolates to be classified into four groups. The polypeptides which varied among the different groups were shown to be located in the surface component of the virion. Unilateral cross reactions detected in cross-neutralization tests were found to correlate with classification of the isolates based on the position of the distinct polypeptide bands. Cross-immunity tests were performed in lambs using two isolates which did not cross-react in the cross-neutralization tests and in which differences in the polypeptide profiles were detected. Reinoculation with virulent sheep-passaged CE viruses overcame the immunity of the lambs. By contrast, there was protection against the less virulent cell culture-passaged CE viruses with cross-protection between the two isolates. These results suggest that virulent CE viral isolates may be responsible for the occurrence of CE in vaccinated animals rather than differences in antigenicity. Two epidemiological aspects of CE infection of sheep were also studied. Latent CE infections were investigated by treating CE-inoculated sheep with corticosteroids. Treatment induced recrudescence of lesions at sites of previous CE virus inoculation, but virus could not be isolated from these lesions. Hence, the existence of latent infections could not be confirmed, but it is unlikely that latent infections are important for the initiation of CE disease outbreaks. Importance of colostral immunity was investigated with ewes vaccinated 6 months prior to parturition. This vaccination did not result in sufficient colostral immunity to protect lambs from subsequent exposure to CE virus, however, the severity of the CE lesions may have been reduced. / Ph. D.