Polyanionic compounds [i.e. pentosan polysulphate, dextran sulphate, heparin, suramin, and aurintricarboxylic acid (ATA)] and castanospermine were examined for their inhibitory effect on human immunodeficiency virus (HIV) strains (HIV-1(IIIB), HIV-1RF, HIV-2ROD and HIV-2EHO) in two different assays (HIV cytopathicity in MT-4 cells and HIV antigen expression in CEM cells). In the MT-4 assay dextran sulphate and pentosan polysulphate were more active against HIV-2ROD, suramin was more active against HIV-1RF, and ATA more active against HIV-2EHO. Heparin was less, but castanospermine was more, active against the two HIV-2 strains. In the CEM assay dextran sulphate and suramin were equally active against all HIV strains, pentosan polysulphate was more active against both HIV-2 strains, whereas heparin was less active against HIV-2ROD and ATA again was more active against HIV-2EHO. The compounds and soluble CD4 (sCD4) were also tested in the HIV-induced syncytium formation assay, where chronically infected HUT-78 cells were mixed with uninfected MOLT-4 or CEM cells. The inhibitory effect of suramin and ATA on syncytium formation was independent of the virus strain or cell type. For dextran sulphate and pentosan polysulphate, it was dependent on virus strain, and for heparin, castanospermine, and sCD4, it was dependent on both the virus strain and cell type.