An all-parallel tetrameric G-quadruplex formed from a DNA/RNA chimera sequence, d(TTA)r(GGG)d(T) ([Chimera(7mer)](4)), and its interaction with heme have been characterized. [Chimera(7mer)](4) was found to be remarkably more stable compared with a G-quadruplex formed from its DNA counterpart d(TTAGGGT), ([DNA(7mer)](4)), despite the structural similarity between them, and the increased stability of [Chimera(7mer)](4) is likely to be due to the formation of interstrand hydrogen bonds between the rG5 2'-OH and rG6 amino NH2 groups. Heme bound selectively to the 3'-terminal G-quartet (rG6 G-quartet) in the rG6dT7 step of [Chimera(7mer)](4) did not exhibit the heme orientational disorder resulting from the formation of two isomers possessing heme orientations differing by 180 degrees rotation about the pseudo-C-2 axis, with respect to the interacting G-quartet, although it is a general feature of heme-DNA complexes. In a complex between heme and [Chimera(7mer)](4), the predominance of one isomer in the heme orientational disorder over the other one is possibly due to contacts between the rG6 2'-OH group of the G-quartet and heme side chain ones. Peroxidase activity of heme bound to a G