A warm auto-antibody with specificity in the Pr blood group system was demonstrated in the serum and red cell eluate of a patient with purine nucleoside phosphorylase (NP) deficiency. The antibody reacted with all cells tested except En(a-) red cells which lack glycophorin A, the major erythrocyte sialoglycoprotein. However, anti-Ena was ruled out by absorption of the antibody with En(a-) red cells. The antibody demonstrated similar serologic characteristics to Pra antibodies, except that those previously described were inactive with protease-treated red cells, while in this case, reactivity was destroyed by papain and ficin but maintained in the presence of trypsin. Inhibition analysis with purified glycoprotein fragments localized the predominant reactive antigen on the MN sialoglycoprotein between amino acid residues 40 and 61. Serologic tests demonstrated its presence in decreased amount on at least one other erythrocyte membrane structure. The serum from another patient with NP deficiency contained an autoantibody similar to the one described here. It may be of interest to explore the association of auto-antibodies to erythrocyte sialoglycoprotein antigens in NP and other immune deficiency states.