The In(Lu) gene, which inhibits the expression of Lutheran blood group antigens by red cells (RBCs), also down-regulates the expression of an 80-kD glycoprotein, In(Lu)-related p80, by both RBCs and a subset of white cells. This study examined the expression of multiple-RBC p80 epitopes by autosomal and X-linked recessive-type Lu(a-b-) RBCs in order to explore the relationship, if any, between expression of In(Lu)-related p80 and Lutheran antigens. Both autosomal and X-linked types of recessive Lu(a-b-) RBCs expressed near-normal to increased amounts of p80 antigens, as measured by radioimmunoassay. P80 from both types of recessive Lu(a-b-) RBCs had apparently normal molecular weight in denaturing polyacrylamide gels and showed normal sensitivity to digestion by trypsin and chymotrypsin. Thus, the absence of Lutheran antigens on recessive-type Lu(a-b-) RBCs is not associated with decreased or absent p80 antigens. Furthermore, the XS2 gene probably does not act via a mechanism similar to that of the In(Lu) gene, since the expression of p80 remains undiminished in X-linked recessive-type Lu(a-b-) RBCs.