This report describes the organization of the mouse pore-forming protein (perforin) gene (Pfp), which is highly analogous to that of the corresponding human gene. Pfp comprises three exons, the first of which consists entirely of 5' non-coding sequence, separated by an intron of 1.94 kb from the two polypeptide-coding exons. The promoter region of the gene shows strong similarity to that in humans, with six stretches of high homology noted within 0.7 kb of the mRNA cap site. However, many of the sequences of the human gene with similarity to previously described promoter/enhancer elements are poorly conserved in the mouse, suggesting that these motifs may be of no functional significance, and that control mechanisms for expression of Pfp may be highly specific to killer cells.