Slices of human femoral cortical bone were prepared with a carborundum wheel. Osteoclasts were isolated from neonatal rabbit long bones and incubated on either untreated, demineralized or anorganic preparations of these bone slices. Anorganic bone showed extensive tracts of uninterrupted surface excavation after incubation, while untreated bone tended to show discontinuous excavations of smaller total volume; demineralized bone was not resorbed. The endosteal surface of adult rat calvaria was also used as a substrate for osteoclastic bone resorption. The endosteal surface was exposed and rendered acellular, and was used either without further treatment or after incubation in collagenase. Bone resorption occurred only in those calvaria pre-treated with collagenase. These experiments imply that osteoclastic contact with bone mineral rather than the endosteal surface is the stimulus that initiates bone-resorptive behaviour in osteoclasts. The mechanism by which osteoblasts induce osteoclastic bone resorption may be through the known ability of osteoblasts to secrete collagenase, which, by digestion of the unmineralized lamina limitans of endosteal surfaces, exposes bone mineral to osteoclastic contact.