The influence of mechanical stimulation by intermittent compressive force (ICF) of physiologic magnitude on osteoclastic bone resorption was investigated in cultures of fetal mouse cartilaginous long bones. Exposure to ICF resulted in a significant decrease in mineral resorption, as indicated by the decreased release of %a and a decreased number of osteoclasts in the diaphysis. Conditioned medium (CM) from ICF-exposed periosteum-free cultures (ICF-CM), but not from control cultures (Co-CM), inhibited mineral resorption in fresh bones cultured under control conditions. Co-CM increased, but ICF-CM decreased, the number of tartrate-resistant acid phosphatase-positive cells in 7-day bone marrow cultures. Direct exposure of bone marrow cultures to ICF yielded the same results. Thus, osteoclastic bone resorption in cartilaginous long bones is inhibited by ICF in vitro. A soluble factor($ acting on tartrate-resistant acid phosphatase-positive, osteoclast precursor-like cells seems to play a role in this effect.Mechanical forces play an important role in the differentiation, growth, and remodeling of the skeleton. An overall decrease in the functional load exerted on the skeleton produces mineral loss and osteoporo-