Successful inhibition of Borna disease virus (BDV) by amantadine in cultured cells and in an infected human individual has been reported [Bode et al. (1997) Lancet 349: 178-179]. We now found that infection of monkey Vero cells by laboratory strains of BDV was not influenced by amantadine under conditions that reduced the yields of influenza A virus by about 400 fold. Amantadine treatment of Vero cells persistently infected with BDV did not result in reduced viral RNA levels, and application of the drug to persistently infected BALB/c mice had no effect on the concentration of BDV in their brains. Thus, susceptibility to amantadine is not a characteristic of BDV, although it may be observed with certain primary virus isolates.