Viraemia then multiple infections of skin epidermis.

Ballooning then necrosis of the epidermal cells of the skin with a proliferation of the adjacent epidermal cells in response to epidermal growth factor encoded by the virus. This proliferation provides the virus with new host cells.

The proliferation, ballooning, and final necrosis (hydropic degeneration) of infected cells gives rise to the classical sequence of lesions seen as papule, vesicle, pustule, and finally, scab. The centre of the pock can become secondly infected. Resolution in 3-4 weeks.

Other poxviruses spread to the upper respiratory tract eg fowlpox and cat pox. More rarely virus will replicate in the viscera giving rise to multiple focal lesions which are often fatal, e.g. sheep pox.