Comment and Summary The infant hamster appears to be the most sensitive host system thus far devised for detection of naturally occurring strains of Machupo virus. Infected brains also serve as a convenient source of CF antigens which can be employed for provisional grouping of hamster pathogenic isolates. Specific neutralizing antibodies can be measured in WI-26 (or other, vide infra) cell cultures. Nevertheless, epidemiological studies of Machupo and related viruses would be facilitated greatly by discovery of a type-specific hemagglutinin (HA) and by development of a cell culture system at least as sensitive as the infant hamster for recovering virus. An added bonus to such good fortune would be the elaboration of viral CF and HA antigens in such a cell culture. The properties of Machupo virus here enumerated do not permit accurate classification of the agent within any of the currently recognized vertebrate virus families. Presence of RNA, however, excludes Machupo virus from the adenovirus, pox virus, papovavirus and herpes simplex virus groups. Inactivation by chloroform eliminates picornaviruses and reoviruses from consideration. In Table 2 the known properties of Machupo virus are compared with properties of other infectious agents, to which biologic groups this virus could conceivably belong. The list is not exhaustive but is intended to serve primarily as a departure for discussion and future work. To date, the virus has not been isolated from an arthropod; thus, the main prerequisite for membership in this family eludes us. Some similarities of the pattern of chronic infection established in hamsters to that of LCM virus in mice made this possibility interesting. Cross CF tests, however, did not disclose any relationship with LCM virus. In addition, CF tests with a large number of myxoviruses also were negative. Attempts to recover pleuro-pneumonia-like organisms (PPLO) from hamster brain virus pools were unsuccessful, but a virus pool grown in WI-26 cell culture did yield a PPLO. Although we believe this to be a cultural contaminant, further studies are in progress. Behavior of agents in laboratory animals and cell cultures is variable and of limited use in classification. It appears that definitive classification of Machupo virus must ultimately be resolved by detailed study of virus size and structure.