Efficient heteronuclear J cross-polarization ( I, 2) in liquids has recently been demonstrated using multiple-pulse sequences instead of spin locking with a single pulse (3-7). These experiments, called heteronuclear isotropic mixing ( 7), HEHAHA, or hetero-TOCSY (6), have been proposed as a preferable alternative to INEPT or DEPT and as a technique for extending total correlation spectroscopy (TOCSY or HOHAHA ) to heteronuclear spin systems (6). Some of this attention has been motivated by the hope (5, 6) that multiple-pulse sequences could slow relaxation in these rotatingframe experiments below a rate of T;j , as has been demonstrated in homonuclear TOCSY experiments (8). It is the purpose of this Note to show that pulse sequences which prolong relaxation in heteronuclear systems lead to inefficient heteronuclear cross-polarization, and that consequently the reasoning behind the choice of mixing sequences must be different in heteronuclear experiments than it is in homonuclear experiments. The term “isotropic” has come to have several meanings in the NMR literature. In homonuclear cross-polarization experiments (TOCSY or HOHAHA), the term has been applied to pulse sequences which eliminate Zeeman terms from the total Hamiltonian, so that in liquids only the J coupling terms remain: