1. Meckel's cartilages and the intramembranous sites of ossification in the mandible, tympanic ring, and the anterior process of the malleus of fetal rats between fifteen and twenty days of intrauterine life have been studied with respect to the localization of alkaline phosphatase during the normal differentiation of embryonic mesenchymal cells to osteoblasts and chondroblasts.

2. Alkaline phosphatase appears in the nuclei concurrent with the preliminary condensation of osteogenic mesenchymal cells in the primordium of an intramembranous ossification center.

3. With further differentiation of these osteogenetic precursors to bone-forming cells, the enzynme appears in the nucleoli and in the cytoplasm. At an osteoblastic stage it also appears intercellularly in the osteoid matrix.

4. Mesenchymal cells that have not differentiated in an osteogenetic direction are free of enzymatic activity in contrast to the mesenchymal osteogenic precursor cells.

5. No enzymatic activity was noted during the condensation and differentiation of mesenchymal cells in a chondrocytic direction until hypertrophy of chondrocytes took Place preparatory to ossification.

6. Enzymatic activity was demonstrable in the ossifying anterior portion of Meckel's cartilage but not in its nob-ossifying portion.

7. The preskeletal type of tissue, an internmediate between bone and cartilage, which may also be called secondary or hypertrophic cartilage, occurs in the ramus of the membranous bony mandible. This is a "neomorphic" product in the differentiation of rapidly proliferating osteogenetic on osteoblastic cells in a site of intramembranous ossification. This is well demonstrated by our studies of alkaline phosphatase activity.