This report characterizes lentivirus attenuation associated with a vif mutation by inoculation of newborn kittens with a vif-deleted feline immunodeficiency virus provirus plasmid (FIV-pPPRDeltavif). Virus in peripheral blood, antiviral antibody or CD4 T-cell count alterations were not detected in kittens inoculated with FIV-pPPRDeltavif plasmid, with the exception of one kitten that demonstrated FIV Gag antibody production at 42 weeks after inoculation. In contrast, wild-type FIV-pPPR-infected kittens were viraemic, seropositive and exhibited a decrease in the CD4 T-cell subset in peripheral blood. Interestingly, FIV-specific T-cell proliferative responses detected at 32 and 36 weeks after infection were comparable for both FIV-pPPRDeltavif- and wild-type FIV-pPPR-inoculated kittens and suggested the possibility of a discreet tissue reservoir supporting sustained FIV-pPPRDeltavif expression or replication. Overall, these findings confirmed that the severe virus attenuation for both replication and pathogenicity exhibited by a vif-deleted FIV mutant is similar for both neonatal and adult hosts.