We prepared hairpins that differ in the connectivity of phosphodiester linkages in the loop (RNA vs 2', 5'-RNA). We find that the stability of the extra stable RNA hairpin 5'-rGGAC(UUCG)GUCC-3' is the same as that observed for the hairpin containing a 2',5'RNA loop, i.e. 5'-rGGAC(UUCG)GUCC-3' (where UUCG = U2'p5'U2'p5' C2'p5'G2'p5'). Also significant is the finding that when the stem is duplex DNA, duplex 2',5'-RNA, or DNA:2',5'-RNA, hairpins with the UUCG loop are more stable than those with UUCG loop.