Experimental infection of piglets with a fecal pool containing hepatitis E virus (HEV) strains Osh-25 and Osh-228 confirmed previous results obtained with HEV strain Osh-205 on susceptibility of these animals to hepatitis E. A biphasic increase of transaminase activities, histopathologic changes in the liver, virus excretion with feces were observed in the animals. The genome of viral particles in piglet feces conformed, at least partially, to human HEV RNA. Ultrastructural abnormalities of piglet hepatocytes resembled those in primates with experimental hepatitis E. The number of positive results (during follow-up of the particles and HEV RNA in various organs of experimental animals) was the highest on day 10 after infection. Both the particles and HEV RNA were present in the lymphoid tissue over the entire follow-up period, from day 5 to day 15 postinfection.