We cloned and determined the DNA sequence of a novel gene (termed RD or D6S45) situated in the class III region of the human major histocompatibility complex (HLA) between the Bf and C4A complement genes. The coding region of the gene is contained in 10 exons spread over approximately 6 kb of DNA. The encoded protein is predicted to contain 371 amino acid residues with a molecular weight of 41,000. The predicted amino acid sequence is notable for a central region containing 24 consecutive pairs of alternating basic (Arg) and acidic (Asp or Glu) residues similar to, but more strictly alternating than, those seen in the 70K protein of the U1 small nuclear ribonucleoprotein (snRNP). There is a high degree of homology both at the amino acid and DNA level between the human RD gene and its murine homology. Although the central region is highly repetitious and contains a high proportion (13%) of CpG dinucleotides-both features that might predispose to frequent mutations-sequence analysis of this region in genes amplified from six individuals revealed no polymorphism.