In an attempt to reproduce experimentally the fulminant hepatitis of pregnant women infected with hepatitis E virus (HEV), 4 nonpregnant and 6 pregnant rhesus monkeys in the first, second, or third trimester of pregnancy were inoculated intravenously with approximately 10(5.5) ID50 of HEV. Comparison of biochemical, histopathologic, and serologic profiles in pregnant and nonpregnant monkeys did not reveal an increase in the severity of hepatitis in the pregnant animals. Hematology and serum clinical chemistry values were in the normal range in all animals during the study. No evidence of neonatal infection with HEV was found in offspring. Two rhesus monkeys (1 pregnant, 1 nonpregnant) had naturally occurring anti-HEV antibodies prior to inoculation as detected by a standard ELISA and confirmed by a competition ELISA with hyperimmune chimpanzee serum. These animals demonstrated an anamnestic response when they were challenged with HEV.