Lysosomotropic compounds (ammonium chloride, chloroquine, amantadine, monensin) effectively inhibited the replication of Pichinde, Mopeia, and Lassa viruses in BHK-21 and Vero cells. The inhibitory effect was dependent upon the time of drug addition and was most effective when the drugs were added 1 h before the viral adsorption. The drugs had no direct effect on the infectious viruses nor on adsorption of the arenaviruses. These results suggest that the arenaviruses enter cells by adsorptive endocytosis with the participation of acidic intracellular vesicules.