Biochemical mechanisms underlying the development of enzymes during mammalian ontogeny are under study. The postnatal development of rat liver and epidermal histidase has been adopted as a model system. Histidase initially emerges in epidermis and liver several days pre- and postnatally, respectively, and undergoes a further multiphasic postnatal developmental course characteristic of each tissue. Various hormonal inducers, e.g., estrogen, glucocorticoid and glucagon (cAMP), and suppressors, e.g., androgen, are capable of regulating histidase differentially at various developmental stages at the two tissue sites, and are responsible for promoting developmental alterations in histidase activity at specific stages in each tissue. The differential expression of histidase catalytic activity in liver and skin during development is due, not to dissociable activators, and/or inhibitors of the enzyme, nor to enzyme variants elaborated during development, but to quantitative alterations of the same enzyme protein during development, as estimated immunochemically. Furthermore, histidase synthetic rates (as measured by pulse incorporation in vivo of radioactively labelled leucine into histidase immunoprecipitates, relative to that into total soluble protein) are altered proportionately to enzyme catalytic activity and quantity during development, increasing in male liver and more markedly in female liver and simultaneously declining in the skin of the same animals. Thus, tissue and sex specific differential development of histidase activity is due to alterations in amounts of the same enzyme protein, tissue and sex specific differential development of histidase activity is due to alterations in amounts of the same enzyme protein, which in turn result from hormonal modulation of histidase synthetic rates. BIBLIOGRAPHIC REFERENCES: Lamartiniere, C.A. and Feigelson, M. Rat liver histidase: purification physical and immunological properties. Abstr., Fed. Proc. 34:641, 1975, (reprint enclosed). Lamartiniere, C.A. and Feigelson, M. Physical, immunologic and catalytic properties of rat liver histidase during postnatal development. Abstr., ICN-UCLA Winter Conferences on Molecular and Cellular Biology, Squaw Valley, Calif., 1975.