Typical acute hepatitis was reproduced in a human volunteer immune to hepatitis A virus (HAV) after oral administration of pooled stool extracts from presumed cases of epidemic non-A, non-B hepatitis. Markers of hepatitis B infection, anti-HAV IgM, and increase in total anti-HAV level were not detectable in the volunteer's sera during the course of infection. Spherical 27- to 30-nm virus-like particles were visualized by immune electron microscopy (IEM) in stool samples collected during preclinical and early postclinical phases. These particles banded in CsCl at a buoyant density of 1.35 g/cm3. They reacted in the IEM test with sera from individuals who had experienced two non-B hepatitis episodes but did not react with sera from routine anti-HAV IgM-positive hepatitis patients. Intravenous inoculation of cynomolgus monkeys with the virus-containing stool extract resulted in histopathologically and enzymatically confirmed hepatitis, excretion of virus-like particles, and antibody response to them.