Hepatitis C (HCV) virus is recognized as the major cause of what was previously referred to as parenterally acquired (blood-mediated) non-A, non-B hepatitis. A study involving 252 transfused and nontransfused Egyptian children was conducted from November 1990 through February 1991 to determine the prevalence of HCV and the role of blood and blood and blood product transfusions in the spread of the virus. Serum specimens were assayed by a second generation enzyme immunoassay and were considered reactive only after supplemental testing using the second generation recombinant immunoblot assay. Prevalence among 84 young study subjects with hematologic disorders was 55% (46 of 84), while no HCV antibodies were detected among the two nonhematologic pediatric populations studied: 84 hospital admissions and 84 acutely ill but otherwise healthy outpatients (seeking treatment for symptoms associated with a new condition less than three weeks old in the absence of any chronic health problem). Ninety-two percent (77 of 84) of the hematology-related cases had medical histories of multiple transfusions. Positive antibody responses (46) were significantly associated with increased duration of illness (P < 0.001) and the volume and number of transfusions (P < 0.01) when compared with negative ones (38). However, prior hospitalization and/or surgery were not related to HCV antibody status. The high prevalence of HCV antibody among multiply transfused infants and children suggests that blood and blood product supplies should be regularly screened for HCV antibody.