The H19 gene in mice was identified as a fetal-specific mRNA under the control of the raf locus. Despite the presence of multiple translation termination signals in all three reading frames, the protein product of this gene could not be detected from its nucleotide sequence. The human H19 gene was cloned and sequenced, revealing no conserved open reading frame (ORF) between the two homologs. Cellular fractionation showed that H19 RNA is cytoplasmic but not associated with the translational machinery. Instead, it is located in a particle with a sedimentation coefficient of approximately 28S. Although transcribed by RNA polymerase II and spliced and polyadenylated, H19 RNA is not a classical mRNA. The product of this gene may instead function as an RNA molecule. The H19 gene is expressed in fetal and neonatal liver and is repressed in adult tissues. It is coordinately expressed with α-fetoprotein (AFP) in the visceral endoderm of the yolk sac and fetal gut. However, unlike AFP, H19 mRNA is also found in fetal skeletal and cardiac muscle. Sequence analysis of the H19 gene revealed multiple small ORFs, none of which spanned more than two exons. The largest ORF, ORF5, could potentially encode a 132-amino-acid protein. However, no evidence suggested that this ORF was translated. The human H19 gene was isolated and sequenced, revealing a structure identical to the mouse gene. The human H19 gene is organized into five exons and four small introns. Sequence comparison between the human and mouse H19 genes showed 77% sequence identity, with the most conserved region located at the 3' end of the first exon. The human and mouse H19 genes share no conserved ORF, suggesting that the gene may not encode a protein. H19 mRNA is not associated with ribosomes, as shown by sedimentation analysis. It is located in a cytoplasmic particle with a sedimentation coefficient of approximately 28S. This is consistent with the interpretation that H19 RNA is complexed with proteins in the cytoplasm. The H19 gene is transcribed by RNA polymerase II, as shown by nuclear run-on experiments. These findings suggest that the H19 gene may function as an RNA molecule rather than encoding a protein. The conservation of the H19 gene between mammals and avian species suggests a common function, which may not necessarily be to encode a protein. Future studies will focus on the nature of the cytoplasmic particle containing H19 RNA and the phenotypic effects of overproducing or deleting the gene.The H19 gene in mice was identified as a fetal-specific mRNA under the control of the raf locus. Despite the presence of multiple translation termination signals in all three reading frames, the protein product of this gene could not be detected from its nucleotide sequence. The human H19 gene was cloned and sequenced, revealing no conserved open reading frame (ORF) between the two homologs. Cellular fractionation showed that H19 RNA is cytoplasmic but not associated with the translational machinery. Instead, it is located in a particle with a sedimentation coefficient of approximately 28S. Although transcribed by RNA polymerase II and spliced and polyadenylated, H19 RNA is not a classical mRNA. The product of this gene may instead function as an RNA molecule. The H19 gene is expressed in fetal and neonatal liver and is repressed in adult tissues. It is coordinately expressed with α-fetoprotein (AFP) in the visceral endoderm of the yolk sac and fetal gut. However, unlike AFP, H19 mRNA is also found in fetal skeletal and cardiac muscle. Sequence analysis of the H19 gene revealed multiple small ORFs, none of which spanned more than two exons. The largest ORF, ORF5, could potentially encode a 132-amino-acid protein. However, no evidence suggested that this ORF was translated. The human H19 gene was isolated and sequenced, revealing a structure identical to the mouse gene. The human H19 gene is organized into five exons and four small introns. Sequence comparison between the human and mouse H19 genes showed 77% sequence identity, with the most conserved region located at the 3' end of the first exon. The human and mouse H19 genes share no conserved ORF, suggesting that the gene may not encode a protein. H19 mRNA is not associated with ribosomes, as shown by sedimentation analysis. It is located in a cytoplasmic particle with a sedimentation coefficient of approximately 28S. This is consistent with the interpretation that H19 RNA is complexed with proteins in the cytoplasm. The H19 gene is transcribed by RNA polymerase II, as shown by nuclear run-on experiments. These findings suggest that the H19 gene may function as an RNA molecule rather than encoding a protein. The conservation of the H19 gene between mammals and avian species suggests a common function, which may not necessarily be to encode a protein. Future studies will focus on the nature of the cytoplasmic particle containing H19 RNA and the phenotypic effects of overproducing or deleting the gene.