SUMMARY: The multiplication of ectromelia virus in mouse liver cells has been studied using intravenous inocula of 106 to 1010 LD50 doses. About 30% of this virus is found in the liver in 5 min., and most of this disappears as infective virus in the next hour. After a lag period, the length of which depends on the number of LD50 doses/cell which initiated the infection, the virus titre increases again to the 5 min. level. Subsequently, steps of multiplication, each separated by a lag period, occur within each cell. The efficiency of virus multiplication over the range tested is independent of the infecting dose.