We are studying the effect of iron, hematin and prophyrinogenic agents on the rate-limiting enzymes of the heme biosynthetic pathway. These experiments are being conducted in iron-deficient rats. Investigations in humans concern the rate of bilirubin formation in porphyrias after hematin injection. Studies in vitro will be initiated which bear on the mechanisms of transfer of iron and porphyrins across the mitochondrial membrane and the effect of chelators on these processes. These studies are directed toward the development of tools to assess the efficacy of treatment in iron overload and porphyrias. BIBLIOGRAPHIC REFERENCES: Liem HH, Miyai K, and Muller-Eberhard U: Effect of porphyrinogenic agents on protein synthesis and bilirubin formation by the isolated perfused rat liver. Biochimica et Biophysica Acta 496:52-64, 1977. Cripps DJ, Liem HH, and Muller-Eberhard U: Griseofulvin, a potent inducer or porphyric hepatomas and hyperhemopexinemia in mice. An in vivo and in vitro study. Journal of Investigative Dermatology 68:82-87, 1977.