We evaluated the performance of a monoclonal radioimmunoassay (M‐RIA) with enhanced sensitivity and high specificity for hepatitis B surface antigen (HBsAg) in blood donors. The results were compared to a conventional RIA that used polyvalent antibodies (P‐RIA). Analysis of 6409 American blood donors not reactive by P‐RIA revealed an additional 1.4 HBsAg‐positive donors per 1000 by M‐RIA, or an approximate 60 percent, improvement in HBsAg detection rate. Furthermore, in 995 Israeli blood donors negative by P‐RIA, 11 additional HbsAg‐positive donors were identified. The 55 percent improvement in detection rate was similar to that observed with American blood donors. Since several of the newly identified HBsAg‐positive blood donors had antibodies to the core antigen (anti‐HBc) as the only serologic evidence of recent or past hepatitis B exposure, we studied an additional 68 anti‐HBc‐ positive individuals with the M‐RIA. It was found that 26 percent (18/68) reacted only by M‐RIA and not by P‐RIA. These findings suggest that there are blood donors with