There is considerable controversy as to whether antigens of the Rh, Duffy, Kidd, Kell, or Lutheran red cell systems are present on human platelets. The majority of previous investigators of this topic have reported them to be present. We have used a sensitive two-stage radioimmunoassay to examine human platelets for the presence of antigens of these five red cell systems. Platelets from donors of appropriate red cell phenotype were incubated with monospecific anti-erythrocyte IgG, followed by a second-stage incubation with 125I-labeled mouse IgG monoclonal anti-human IgG (Fc). Analysis of ligand bound per cell demonstrated no significant difference in binding of erythrocyte antibodies to platelets from donors homozygous, heterozygous, or negative for D, C, c, E, e, Fya, Fyb, Jka, Jkb , K, k, and Lub antigens. These findings indicate that major antigens of the Rh, Duffy, Kidd, Kell, and Lutheran systems are not expressed on the surface of human platelets.