The organic plant extracts of 21 species of Clusiaceae from Mexico were screened for anti HIV-1 reverse transcriptase activity in a non-radioactive immuno colorimetric assay. The extracts of 5 species (23.8%) exhibited significant inhibition (≥70%) of HIV-1 RT activity; of these, only 4 extracts showed reduced toxicity to human lymphocytic MT2 cells and were further tested as inhibitors of HIV-1 IIIb/LAV replication in a cellular system. The best extracts were Calophyllum brasiliense (hexane) and Clusia quadrangula (CH₂Cl₂–MeOH) which inhibited HIV-1 RT (IC₅₀=29.6 μg/ml and 42 μg/ml), and showed an EC₅₀=92.5 μg/ml and 91 μg/ml, respectively, on MT2 cells. However, only Calophyllum brasiliense hexane extract showed significant inhibition on viral replication (ED₅₀=37.1 μg/ml), while Clusia quadrangula was less active (ED₅₀=124 μg/ml). These results support the idea that plant extracts represent a valuable source of potential anti HIV compounds.