Screening for hepatitis B (HBV) surface antigen (Ag HBs) and for antibodies to hepatitis C (HCV) and human: immunodeficiency virus (HIV) was carried out in 9006 volunteer blood donors at the National Blood Bank in the Republic of Djibouti from 1998 to 2000. Results demonstrated the presence of Ag HBs in 934 patients (10.4%), antibodies to HCV in 21 patients (0.3%), and antibodies to HIV in 175 patients (1.9%). In comparison with neighboring countries the prevalence of HBV, HCV, and HIV infection in Djibouti was low. These findings should be used to guide preventive action against these viral infections in the Republic of Djibouti. Estimations of HIV infection (11.7%) based on modeling by the World Health Organization should be reviewed.