The serological response of naturally and experimentally infected lambs to orf virus infection was analysed using an enzyme-linked immunosorbent assay (ELISA) together with the Western blotting technique. The combination of these two methods permitted a qualitative and quantitative assessment of the response, which revealed considerable variation between animals. Despite this, all post-exposure sera reacted with a polypeptide (molecular weight 40 kilodaltons) which appears to be a component of the surface tubules that are characteristic of the virus.