SummaryData are presented from serologic screening for human immunodeficiency virus type 1 (HIV-1) in all blood donors (n = 3,696) in Gonder, Ethiopia, between 1989 and 1993. The crude seroprevalence was 10.6% in men (326 of 3,066) and 11.9% in women (75 of 630). Seroprevalence in male donors increased from 3.8% in 1989 to 16.0% in 1993 (p= 0.001); in female donors, seroprevalence increased from 7.0% in 1989 to 16.8% in 1992 (p= 0.002) and decreased to 13.4% in 1993. Syphilis seroreactivity increased from 4.8% in 1991 to 9.2% in 1993 (p= 0.02). HIV-1-seropositive donors were more likely to be seroreactive for syphilis than HIV-1-negative donors (odds ratio = 2.36; 95% confidence interval, 1.73–3.22). Therefore, there is an urgent need for control programs for both infections.