A series of 1,3-thiazolidin-4-ones and metathiazanones were synthesized and evaluated as anti-HIV agents. The results of the in vitro assays showed that some of the synthesized compounds were effective inhibitor of reverse transcriptase enzyme of human immunodeficiency virus type-1 (HIV-1) at micromolar concentrations with less cytotoxicity in MT-4 cells as compared to thiazolobenzimidazole (TBZ). Structure-activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidin-4-one nucleus had a significant impact on the in vitro anti-HIV activity of this class of antiretroviral agents. One of the compounds, 1, inhibited the enzyme at 0.204 microM concentrations with minimal cytotoxicity to MT-4 cells.