Enterovirus 70 (EV70), like several other human enteroviruses, can utilize decay-accelerating factor (DAF [CD55]) as an attachment protein, Using chimeric molecules composed of different combinations of the short consensus repeat domains (SCRs) of DAF and membrane cofactor protein (CD46), we show that sequences in SCRI of DAF are essential for EV70 binding. Of the human enteroviruses that can bind to DAF, only EV70 and coxsackievirus A21 require sequences in SCR1 for this interaction.