Several compounds, belonging to different classes of nucleoside analogues and sulfated polysaccharides, were evaluated for their inhibitory effects on the replication of the arenaviruses Junin and Tacaribe in VERO cells. S-Adenosylhomocysteine (AdoHcy) hydrolase inhibitors [i.e. adenosine dialdehyde, carbocyclic 3-deazaadenosine (C-c3 Ado), neplanocin A, 3-deazaneplanocin A, 9-(2,3-dihydroxypropyl)adenine [(S)-DHPA], (RS)-3-adenin-9-yl-hydroxypropanoic acid isobutyl ester [(RS)-AHPA], the 2',3'-dihydroxycyclopentenyl derivatives of adenine (DHCA) and 3-deazaadenine (DHCDA)] inhibited arenavirus replication within the concentration range of 1-10 micrograms/ml, while not being toxic for cell morphology or cellular DNA synthesis at a concentration of 100-400 micrograms/ml. Based on the ratio of the concentrations required to inhibit cell proliferation and virus replication, only (S)-DHPA, DHCA, C-c3 Ado and adenosine dialdehyde could be considered as truly selective inhibitors. Tubercidin, cyclopentenyl cytosine, pyrazofurin and ribavirin also inhibited viral cytopathogenicity at concentrations that were well below the cytotoxic threshold. Carbodine (cyclopentyl cytosine) also proved to be a potent inhibitor of arenavirus replication, but it was not as selective as cyclopentenyl cytosine. Very potent and selective inhibitors were the sulfated polysaccharides dextran sulfate, lambda-carrageenan, fucoidan, heparin and pentosan polysulfate: they inhibited virus replication at a concentration of 0.1-2.8 micrograms/ml, whereas the compounds were not inhibitory to cell growth even at a concentration of 200 micrograms/ml.