The lung is an important target organ for HIV infection and AIDS associated disease. Pulmonary infection by opportunistic microorganisms is a major cause of morbidity and mortality in AIDS patients. We have carried out an investigation which has enabled us to distinguish genotypic differences between HIV proviral DNA variants from blood and alveolar leukocytes. Bronchoalveolar lavage and heparinised peripheral blood were collected from HIV positive patients undergoing investigation for respiratory complications. Adherent and non-adherent cell populations were separated and HIV proviral DNA was extracted from each population1. Heteroduplex Mobility Assay (HMA), a PCR-based analysis, was used to distinguish the genotypic variations in the V1 to V5 region of env gene in the different HIV proviral populations2. Significant variation was seen in the env gene of HIV-1 proviral populations from blood and lung in 16 of 27 AIDS patients. In conclusion, using HMA we have been able to distinguish different genotypes in peripheral blood and alveolar leukocytes. This suggests that HIV in target organs such as lung may evolve independently of viruses in peripheral blood. This observation is important for vaccine development to take account of HIV variants in different organs.