The purpose of this work was to elucidate the pathogenesis of attenuated Junin virus (JV) strains in the guinea pig model. Three groups of guinea pigs were infected by the IM route with 10(3) PFU of the XJC13 and XJO-attenuated strains or with the XJ pathogenic strain of JV, respectively. Viremia was studied at 3, 5, 7, 9, 12, and 14 days postinfection (pi) (a) in serum samples of all animals and in washed cells from XJC13-infected guinea pigs by conventional techniques and (b) in whole blood samples from XJC13 and XJO animals by coculture with Vero cells. Virus spread was studied at 14 days pi in brain, spleen, lymph nodes, and bone marrow by parallel suckling mouse inoculation or organ homogenates and coculture of cell suspensions with Vero cells. By coculture techniques of whole blood, an otherwise undetectable viremia was demonstrated for both attenuated strains throughout the observation period. In contrast, XJ viremia was easily detected by direct techniques, as has already been shown. Attenuated virus was also shown to reach brain and bone marrow when coculture methods were employed. But titers were always markedly lower than those of the pathogenic strain. The sustained viremia demonstrated in guinea pigs infected with either attenuated strain explains the mode of viral dissemination and accounts for viral rescue and antigen detection from some organs. These results suggest that attenuated strains do not differ greatly in their invasive capacity in guinea pigs, but later on viral replication is impaired. Therefore, these findings reveal potential risks and should be noted when developing human vaccines.