Three naturally occurring cases of cowpox virus infection in the domestic cat are described. Isolate L97 was identified as cowpox virus on the basis of morphology, serology and characteristic cytopathic effect in tissue culture and on the chorioallantoic membrane of embryonated eggs. All three cases showed multiple skin lesions, slight conjunctivitis or purulent ocular discharge but there were no respiratory signs. Two animals recovered, the third was put down as a stray. The disease was reproduced in experimental cats. Isolate L97 was inoculated into two cats intravenously and two cats by skin scarification. All four developed skin lesions at the site or sites of inoculation, and in one cat multiple lesions developed. The two intravenously inoculated animals also developed severe oedema of the neck and brisket around the site of inoculation into the jugular vein, and one cat died. Serological and pathological findings on both the natural and experimental infections are described. Serum neutralising antibody titres in both natural and experimental early convalescent cases were significantly enhanced by the addition of complement.