To determine and correlate the liver function profile, hepatitis C virus (HCV) genome, anti-HCV, genotypes, quantitation, and nucleotide sequence variability in polytransfused thalassemic children, 61 such children were studied prospectively for 4 y. Twenty-six had HCV infection. The average age, number of transfusions, and alanine aminotransferase (ALT) levels of the HCV-infected group were higher than those of the 35 children without HCV infection. None was infected after the initiation of anti-HCV screening in donor blood. Liver biopsies were performed in six HCV-infected and eight HCV-noninfected thalassemic children, and portal fibrosis was found more frequently in the HCV-infected group. Quantitation of HCV RNA was done by the competitive polymerase chain reaction method, and the titer was about 1 x 10(6) to 5 x 10(8) copies/mL. The titer did not change significantly over the 4-y follow-up period and did not correlate with ALT levels. Nineteen HCV-infected patients were genotyped; 15 were Okamoto/Simmonds type II/1b, two were type III/2a, and two were type IV/2b. The hypervariable region of the HCV genome (E2/NS1) was cloned and sequenced in two serum samples from one patient collected at a 2-y interval, as the ALT levels decreased. The variation rate was estimated to be 1.2-1.7 x 10(-2)/nucleotide/y. The results showed that, in polytransfused thalassemic children, 43% (26/61) contracted HCV. We conclude that HCV infection may cause elevated ALT levels and portal fibrosis of the liver, whereas the viral titer and genotypes do not parallel ALT levels.