The SIV-newborn rhesus macaque model of pediatric aids allows rapid evaluation of the virulence of viral variants and of the efficacy of antiviral drug therapy. To determine the virulence of AZT-resistant viruses, four newborn macaques were inoculated intravenously with a biological clone of AZT-resistant SIVMAC. Two of these animals were also treated orally with AZT, at a dosage regimen previously shown to have strong therapeutic effects against AZT-sensitive SIVMAC. All four animals showed persistent infection, and two out of four animals developed fatal disease within ten months after inoculation (one untreated animals died at twelve weeks, and one AZT-treated animal died at eight months). No reversion from AZT -resistance to AZT-sensitivity was observed. These results demonstrate that AZT-resistance is compatible with full pathogenicity, and suggest that AZT-resistant viral mutants may be directly responsible for disease progression despite AZT therapy.