We investigated the course of distinct episodes of acute non-A, non-B (NANB) hepatitis in three polytransfused thalassaemic children. In each case, the first episode was associated with the appearance of serum hepatitis C virus (HCV) RNA and anti-HCV seroconversion. The second episode was accompanied by the reappearance of HCV viraemia, which in two patients was due to reinfection with a different HCV strain and in the third could be the result of either reactivation of primary infection or reinfection with a new but closely related strain. Thus HCV infection may not induce protective immunity, which has implications for vaccine development.