We determined the prevalence rate of hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV) among 7897 healthy voluntary blood donors in Shiraz, Islamic Republic of Iran. Sera were examined for HBsAg and anti-HCV antibodies using a second-generation enzyme-linked immunosorbent assay. Positive sera for HBsAg were found in 85 (1.07%) of the individuals and anti-HCV antibodies were found in 47 (0.59%). We compared our results with those of other studies and conclude that the prevalence rate of HBsAg in our area has decreased in the last 2 decades; from being an area of high prevalence, it is now one with moderate-to-low prevalence. Since there are few reports on the seroepidemiology of hepatitis C in the Islamic Republic of Iran, we could not assess the changes in prevalence of hepatitis C.