In early 1988, an increased incidence of acute hepatitis was observed in villages along the Shebeli River in the Lower Shebeli region of Somalia. This was followed by a large epidemic that lasted until late 1989. In a survey of 142 villages with a population of 245,312 individuals, 11,413 icteric cases were recorded, of which 346 died, corresponding to an attack rate and a case fatality rate of 4.6% and 3.0%, respectively. The etiologic role of hepatitis E virus (HEV) in this epidemic was proven by demonstrating anti-HEV in 128 of 145 sampled cases as a sign of recent infection with HEV. In three villages, where a special study protocol was implemented, the attack rate was found to increase significantly with age from 5% in the group 1-4 years of age to 13% in the group 5-15 years of age and to 20% for persons older than 15 years of age. Among cases 20-39 years of age, the female-to-male ratio was 1.5:1, which was a significant predominance of females. As in other hepatitis E outbreaks, there was a high fatality rate in pregnant females, estimated to be 13.8%. The epidemic peaked with the rise in the level of the river during rainfall, suggesting that the disease was waterborne. The attack rate was higher (6.0%) in villages supplied with river water, while fewer cases were recorded in those relying on wells or ponds for their water supply, 1.7% and 1.2%, respectively. In contrast, cases were more severe and had a higher case fatality rate (8.6%) in villages supplied by wells compared with those relying on river or pond water, 2.5% and 0.8%, respectively. This discrepancy was presumed to reflect the inoculum size of infection made possible with water from wells when the latter were contaminated. In the three villages subjected to a special study, person-to-person transmission within family compounds did not seem to be an important factor since 74.5% of the cases in affected compounds occurred less than one month after the first case, and another 6.8% during the second month; thus, the majority were not likely to be secondary cases.