OBJECTIVE One hundred and eleven patients with acute hepatitis and 61 controls were investigated for hepatitis serological markers in order to determine the viral etiology of cases involved in a waterborne epidemic of hepatitis observed in 1993 in Djibouti, Republic of Djibouti (East Africa). These cases occurred both in indigenous Djiboutians, and in French soldiers and their families in Djibouti. A retrospective study of the viral etiology of acute hepatitis cases observed in French soldiers and relatives living in Djibouti during the 3-year period preceding the epidemic was also undertaken. METHODS HAV, HBV and HCV infections were investigated using commercial ELISA tests. HEV infections were investigated by testing IgG and IgM-specific antibodies by means of three different ELISA tests using recombinant proteins or synthetic peptides. RESULTS Hepatitis A was observed in 37 (33%) and hepatitis E in 43 (39%) of the 111 cases of acute hepatitis recorded during this epidemic. Hepatitis B represented only 6% of the indigenous cases and hepatitis C was not observed among the cases investigated. Anti-HEV IgG antibodies were also detected in 19% of the indigenous control group. CONCLUSIONS These results suggest that both HAV and HEV were responsible for this waterborne epidemic of acute hepatitis. However, HAV and HEV infections were not equally distributed between French expatriates and Djibouti residents. Whereas HAV infections were mainly observed in French patients, HEV was almost exclusively found in indigenous patients. This study reports for the first time a waterborne outbreak of acute hepatitis simultaneously due to HAV and HEV.