R. Tenhunen,% H. Marver, § N. R. Pimstone, If WF Trager, David Y. Cooper, and R. Schmid* abstract: A microsomal enzyme system has been described that converts heme (ferriprotoporphyrin IX) to the linear tetrapyrrole biliverdin IXa. On the basis of its absolute re-quirement for NADPH and molecular oxygen, its sensitiv-ity to inhibition by CO, and its appropriate stoichiometry, the enzyme system tentatively was classified as microsomal heme oxygenase. It now has been demonstrated that bili-rubin formed enzymatically from heme in the presence of molecular lsO-> contains 2 atoms of I80 and an additional isO atom appears in the CO that originates from the a-meth-ene bridge carbon of the heme. No 180 is incorporated into the bile pigment when the enzymatic reaction is carried out in a medium containing H2lsO instead of the molecular 1S02.