Two proteins of apparent molecular weights of 28,000 and 50,000 daltons were shown to recognize and cross-link specifically to the 5′ cap end of oxidized reovirus mRNA. Cross-linking of these proteins to mRNA was ATP/Mg^′′ dependent, in sharp contrast to cross-linking of a 24K cap binding protein which was purified and characterized previously (Sonenberg, N., Rupprecht, K.M., Hecht, S.M. and Shatkin, A.J. (1979) Proc. Natl. Acad. Sci. USA 76, 4345-4349). Non-hydrolyzable analogues of ATP as well as other nucleotides did not substitute for ATP in the cross-linking reaction and Mg⁺⁺ was significantly preferred over other divalent cations in cross-linking of the 28K and 50K dalton proteins. A model involving the function of the latter proteins in recognition and unwinding of the 5′ end structure of capped eu-karyotic mRNAs is suggested.