Man's susceptibility to the virus of foot- and-mouth disease (FMD) was debated for many years. Today the virus has been isolated and typed (type O, followed by type C and rarely A) in more than 40 human cases. So no doubt remains that FMD is a zoonosis. Considering the high incidence of the disease (in animals) in the past and in some areas up to date, occurrence in man is quite rare. In the past when FMD was endemic in Central Europe many cases of diseases in man showing vesicles in the mouth or on the hands and feet were called FMD. The first suggestion of a human infection with FMD was reported in 1695 by Valentini in Germany [7]. All reports before 1897, the year of the discovery of the virus of FMD by Loeffler and Frosch [2], were not of course confirmed either by isolation of the virus or by identification of immunoglobulins after infection. Nevertheless the successful self-infection reported by Hertwig in 1834 most likely seems to have been FMD in man: each of three veterinarians drank 250 ml of milk from infected cows on four consecutive days. The three men developed clinical manifestations. The diseases most often confused with FMD are infections with several viruses of the Coxsackie A group (this infection is referred to as "hand and mouth disease"), herpes simplex and sometimes vesicular stomatitis. Beginning in 1921 up to 1969 at least 38 papers were published, which described clinically manifest FMD in man in more than 40 proven cases. One further reported described an asymptomatic infection with FMD in man [10]. Criteria for establishing a diagnosis of FMD in man are the isolation of the virus from the patient and/or identification of specific antibodies after infection. Laboratory tests for diagnosis of human FMD are the same as for animals. Proven cases of FMD in man have occurred in several countries in Europe, Africa and South America. The type of virus most frequently isolated man is type O followed by type C and rarely A. The incubation period in man, although somewhat variable, has not been found to be less than two days and rarely more than six days.