During December 1993 and in the first three months of 1994, an explosive water-borne epidemic of hepatitis E virus (HEV) occurred in two sectors of Islamabad, Pakistan. In a survey of a population of 36,705 individuals, a total of 3,827 cases of acute icteric hepatitis were recorded with an overall attack rate (AR) of 10.4%. The etiologic role of HEV in the epidemic was proven by demonstrating anti-HEV IgG and HEV IgM in the tested serum samples. The water-borne nature of the epidemic was suggested by a study of the case distribution according to water supply. Prior to the epidemic, there had been an operational breakdown in a water treatment plant that distributed water to the affected areas while transforming its purification system from slow sand to rapid sand filtration. The primary source of water for the plant was derived from a heavily contaminated stream. The highest AR (16.3%) was observed in the areas where the source of drinking water was exclusively from the purification plant, followed by ARs of 12.4% and 5.3% for those receiving 50% and 30% or less of their water supply from the treatment plant, respectively, while the lowest AR (1.8%) was observed in the neighboring areas that did not receive water from this source. The AR was significantly higher in the group 11–30 years of age (15.3%) as compared with children less than 11 years of age (1.4%) and also relative to the group greater than 30 years of age (10.5%). The AR among the 162 recorded pregnant females was 21.6%, which was higher than that found among nonpregnant females of child-bearing age (10.9%). All four reported adult deaths occurred among females in their third trimester of pregnancy with a case fatality rate of 11.4%, while the other four fatal cases were newborn infants of mothers with acute icteric hepatitis. Although the aggregation of cases within households was significantly related to family size, the temporal relationship between cases in households with two or more cases revealed that 83.7% of 1,463 presumed secondary cases occurred within one month of the first case in the same household, which is not suggestive of person-to-person transmission of disease. The termination of providing water from the source was effected, which was followed by an apparent decrease in cases.