Osteoclasts, isolated and purified from the medullary bone of calcium-deficient egg-laying hens, adhere to glass coverslips in vitro by means of specialized protrusions of the ventral membrane, denoted podosomes. These structures represent dotlike close-contact adhesion sites in which most cytoskeletal proteins involved in linking the plasma membrane to microfilaments are organized according to a specific and previously described pattern also shared by many oncogene-transformed cells. We show now that podosomes are not only a feature of osteoclasts adhering to artificial glass surfaces but are also present in the ventral membrane of osteoclasts adhering to bone laminae. Moreover, the quantity and the topography of podosomes may be modulated by retinol, which increases bone-resorbing activity of osteoclasts both in vivo and in vitro. A comparative transmission electron microscopy study of osteoclasts adhering on bone laminae in vitro or in vivo indicates that podosomes with identical features are present in the clear zone of the osteoclasts in either condition. Since podosomes are the sealing structures of the clear zone, podosome formation may represent one of the modifications involved in the reorganization process of the osteoclast that precedes bone resorption.