PBMC and vaginal cell (VC) viruses were studied from 5 HIV-infected females for the presence of drug-resistance and non-drug resistance associated mutations. A 1318-bp fragment of polymerase gene was amplified from PBMC and VC proviral DNA. Four of the 5 PBMC viruses exhibited drug resistance-associated mutations in reverse transcriptase and protease genes, whereas only 2 VC viruses contained drug resistance-associated mutations. However, all 5 females showed non-drug resistance-associated mutations both in PBMC and VC virus suggesting continuous evolution of the virus in these compartments. The emergence of drug resistance was slower in PBMC and VC viruses than that observed in the cell-free plasma (P) and vaginal secretion (VS) viruses. Phylogenetic analysis revealed that VC virus was closer to PBMC virus than either cell-free viruses (P and VS) suggesting comparable evolution among cell-associated viruses.