This study has attempted to clarify the processes of cartilage-to-bone replacement in endochondral bone formation of long bones. Three-week-old male beagle dogs were perfusion-fixed with buffered glutaraldehyde, and dissected distal humeri were examined by means of light and electron microscopy. Calcification of growth plate cartilage occurred in the central area of the longitudinal septa, but not in thin transverse septa. Chondrocytic lacunae were opened by the removal of transverse septa by perivascular mononuclear cells. These cells contained many RER cisterns, well-developed Golgi apparatuses, dense bodies, and pale vesicles, and they had developed membrane ruffling toward the transverse septa. Phagocytosis of cartilage fragments of longitudinal septa was also observed in mononuclear cells lacking membrane ruffling. A thin bone layer was deposited on the remaining longitudinal septa by invading osteoblasts. Osteoclasts in these lacunal canals lacked ruffled borders on the cartilage matrix, but formed these structures on the bone layer deposited on the longitudinal septa. Our results suggest sequential processes in the cartilage-to-bone replacement in growth plates : 1) removal of the transverse septa by perivascular RER-rich mononuclear cells, 2) formation of wider lacunal canals by phagocytosis of cartilage fragments in the longitudinal septa by mononuclear cells, 3) bone deposition over the remaining longitudinal septa, and 4) resorption of calcified cartilage and bone by differentiated osteoclasts.