We have isolated and characterized cDNA and genomic clones containing the mouse apolipoprotein C1 (Apoc1) gene. The Apoc1 gene is part of the Apoe-c1-c2 gene cluster and is located 3.4 kb 3' of the Apoe gene. The mouse Apoc1 gene spans a region of approximately 3.3 kb and consists of four exons. The exon-intron structure is similar to those of human and baboon genes, although in mouse introns 2 and 3 are smaller. Significant sequence homology is found between man and mouse in the promoter and exonic regions (80 and 67%, respectively). Northern blotting and primer extension analysis of mouse RNA showed that a major transcript 409 bp in size is expressed primarily in fetal and adult liver. The mouse Apoc1 cDNA contains an open reading frame encoding a protein of 88 amino acids, including a signal peptide of 26 amino acid residues. Comparisons of the deduced amino acid sequence of mouse apoC1 with the human, baboon, rat, and dog sequences showed discrete regions with a high degree of conservation. The delineation of the sequence and structural organization of the mouse Apoc1 gene is an essential step in enhancing the use of mouse models to study the function of apoC1 in the lipoprotein metabolism.