The recent description of chronic hepatitis E in organ transplant recipients deserves increased awareness in the context of hepatitis E virus (HEV) infection in immunocompromised individuals. Reported here is what is apparently the first PCR-documented case of acute hepatitis E in a human immunodeficiency virus (HIV)-1-infected patient. The CD4(+) T-lymphocyte count was 246/mm(3). The IgM anti-HEV antibody and HEV RNA tests results from serum were positive. Hepatitis was benign, and chronic HEV infection was ruled out. The HEV genotype was 3f. The patient did not report recent travel abroad. HEV should be tested in HIV-infected individuals presenting with acute hepatitis. HEV RNA detection is useful in diagnosing HEV infection and in monitoring recovery.