A new macromolecular catalyst, which is composed of nonnatural ribonucleotide, was synthesized by the in vitro selection (SELEX) method. A pool of RNAs consisting of random sequences was obtained by transcription from a pool of synthetic random-sequence DNAs in the presence of 2'-aminocytidine triphosphate (2'-amino-CTP) instead of CTP. The pool was incubated with N-methylmesoporphyrin-immobilized gel; bound nonnatural RNAs were then collected and amplified by reverse-transcription following the polymerase chain reaction. The amplified DNAs were again transcribed in the presence of 2'-amino-CTP and applied to the gel. This selection process was repeated 10 times. The selected RNAs were cloned and sequenced. The RNAs not only bound to the ligand, N-methylmesoporphyrin but also catalyzed the metalation reaction of porphyrin.