Significance PMPA-resistant SIV mutants arise in SIV-infected macaques following prolonged PMPA treatment. Although we have previously shown that these mutants are highly virulent for newborn macaques, it is unknown whether they are also infectious following mucosal (oral) virus inoculation. Objectives We determined whether the highly virulent PMPA-resistant SIV mutant, designated SIVmac055 can infected juvenile macaques following oral inoculation.. Results All 4 animals which were given 2 doses of SIVmac055 became infected. Our results demonstrate that PMPA-resistant SIV is infectious following oral inoculation. Future Directions Future studies can use the oral route of SIVmac055 inoculation for designing intervention studies aimed at preventing or modulating mucosal infection with PMPA-resistant virus. These studies are relevant with regard to vertical transmission of HIV. KEYWORDS PMPA, oral, primate, drug resistance