In this study, we describe the identification and cloning of a novel member of the nuclear receptor superfamily. This orphan receptor, referred to as ROR gamma, belongs to the ROR/RZR subfamily. The open reading frame of ROR gamma encodes a protein of 560 amino acid residues with a predicted molecular mass of 63 kD. The amino acid sequence of ROR gamma exhibits a 50 and 51% identity with those of ROR alpha/RZR alpha and RZR beta, respectively, whereas the DNA-binding domains were 89% identical. ROR gamma was localized on human chromosome 1. Northern blot analysis using RNA from multiple tissues indicated that ROR gamma is expressed in several tissues but is most highly expressed in skeletal muscle.