The complete amino acid sequence of human prostaglandin endoperoxide synthase (EC 1.14.99.1, cyclooxygenase) was deduced by cloning and sequence analysis of human genomic DNA coding for the enzyme. The isolated clones covered approximately 40 kilobase pairs of human gene and the protein coding region of the enzyme was distributed into eleven exons, which encoded 599 amino acid residues with a calculated molecular weight of 68,548. Human prostaglandin endoperoxide synthase exhibited 91% amino acid identity with the sheep enzyme.