Newborn hamsters inoculated intrahepatically were highly susceptible to infection by axenically cultured Entamoeba histolytica. Inoculations were performed through the abdominal wall, and lesions could be observed through the skin as early as 4 days after inoculation. The most virulent amebal strain, HM-1:IMSS, produced liver lesions in 19% of newborn animals inoculated with 20 amebae, and in about 90% receiving 2,000 amebae. Eleven other strains similarly tested either produced no lesions with 20,000 amebae or were of intermediate virulence. Two hamster strains did not show appreciable differences in susceptibility to the HM-1:IMSS amebal strain. Newborn hamsters were more susceptible to HM-1:IMSS amebae than animals which were 2, 4, or 7 days old at the time of inoculation. Three-week-old animals were resistant to doses below 20,000 virulent amebae.