Biochemical mechanisms underlying the development of enzymes during mammalian ontogeny are under study, adopting the postnatal development or rat liver and epidermal histodase as a model system. Histidase initially emerges in epidermis and liver several days pre and postnatally, respectively, undergoing a further multiphasic divelopmental 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 and at the two tissue sites, and are responsible for promoting alterations in histidase activity at specific developmental stages in each tissue. Hepatic histidase has been pruified to homogeneity and crystallized. The native enzyme is 200,000 molecular weight and can be dissociated into a single subunit species of 70,000 molecular weight; thus native oligomeric rat liver histodase consists of threeidentical subunits. Employing a monospecific antibody to rat liver histidase, immunological studies indicate that histidase from male and female rat skin and liver, rabbit and hamster liver, human normal and malignant liver, but not Pseudomonas, are immunologically identical. 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 the enzyme variants elaborated during development, but to quantitative alterations of the same enzyme protein during development, as estimated immunochemically.