In a prospective study of 287 patients who received blood transfusion, 26 who were found positive for hepatitis C antibody (anti-HCV) by an enzyme-linked immunosorbent assay (ELISA) were studied by a recombinant immunoblot assay (RIBA). Nineteen of the 26 patients had posttransfusion non-A, non-B (NANB) hepatitis. Sixteen (84.2%) of the 19 patients with hepatitis had positive results by RIBA, 2 had indeterminate results, and 1 was negative. By contrast, five of the 7 recipients without hepatitis were negative, 1 indeterminate, and 1 positive by RIBA. Those with negative RIBA results had significantly lower optical density (OD) readings by ELISA than those with positive RIBA tests. Therefore, patients without hepatitis or lower OD value have a higher false-positive rate in anti-HCV ELISA than did those with a high OD value or with evidence of hepatitis.