A clinical disease of hill sheep known as louping-ill has been present in southern Scotland for at least two centuries. Louping-ill virus is recognized to be a member of a closely related complex of tick-transmitted flaviviruses known as the tick-borne encephalitides (TBE). The earliest description of louping-ill refers to a disease prevalent in the Scottish border counties but unknown in the northern uplands. The conventional view that louping-ill is restricted to the British Isles should therefore be accepted with caution until critical comparison of viruses associated with encephalomyelitis of sheep in different geographical areas has been made. Louping-ill, the only flavivirus that has been identified as existing naturally in the British Isles, is a member of a group of viruses distributed primarily throughout the northern temperate latitudes and known as the TBE complex. The transmission of louping-ill virus to laboratory mice by intracerebral inoculation provided the first practical method of assay for both virus and antibody to the virus.