Objective: To evaluate the rate of seropositivity to hepatitis B and C and human immunodeficiency virus (HIV) infections among children with beta-thalassaemia major receiving multiple transfusions in Shiraz, Iran, compared with healthy controls. Methodology: The study was performed during 1999-2000 on multitransfused children with beta-thalassaemia major registered by the Shiraz Thalassaemia Society. Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies (Ab) and HIV Ab were checked using a second-generation enzyme-linked immunosorbent assay (ELISA). Positive tests were confirmed by western blots. Healthy blood donors were used for the control group. Results: Hepatitis B surface antigen, anti-HCV Ab and HIV Ab were positive in four of 755 (0.53%, 95% confidence interval (CI) = 0.17-1.3), 73 of 466 (15.7%; 95% CI = 12.6-19.2) and none of 466 patients tested, respectively. Positive sera for HBsAg, anti-HCV Ab and HIV Ab were found in 85 (1.07%), 47 (0.59%) and 27 (0.34%) of 7879 control children, respectively. The rate of anti-HCV Ab was significantly higher in patients than in the control group (P < 0.0001). In patients, the rate of positive anti-HCV Ab was significantly higher than the rate for positive HBsAg (P < 0.0001). Conclusion: It is concluded that HCV is the current major problem in multitransfused children with thalassaemia major and more careful pretransfusion screening of blood for anti-HCV must be introduced in our blood banks.