Alanine aminotransferase (ALT), v-glutamyl-transferasc and hepatitis B core antibodies were evaluated as donor markers in a prospective study of 685 open-heart surgery patients. Of these three surrogate markers, only an ALT level greater than or equal to 2 SD above the log mean had a significant association with recipient non-A, non-B hepatitis (NANBH, p = 0.02). Antibodies to the hepatitis C virus (anti-HCV) were detected by an enzyme immunoassay in 7 of the 136 units transfused to the 11 NANBH patients and 29 of 3,650 not associated with hepatitis (p<0.001). Calculated from this subgroup of donors, the anti-HCV test would have a 15.6% positive predictive value with 0.92% donor loss and thus is superior as a primary screening marker to all the three surrogate tests. The predictive value could be substantially increased by subsequent ALT testing or by the use of a recombinant immunoblot anti-HCV assay.