The effect of acetylsalicylic acid (aspirin) on bone mass and bone prostaglandin E (PGE) in immobilization osteoporosis was studied in 12 growing dogs using a unilateral hind limb cast-fixation model. Osteoporosis was induced by fiberglass-cast immobilization of the right hind limb for 4 weeks, with the left hind limb as a control. Six dogs received buffered aspirin at 25 mg/kg body weight per os every 8 hours; 6 dogs received no treatment. All the dogs were killed after 4 weeks, and bone samples were collected. Bone mineral content of the distal tibial metaphysis was measured by single-photon absorptiometry. In vitro release of PGE from the calcaneus, tibial cortical bone, tibial cancellous bone, and ilium were measured using a specific radioimmunoassay for PGE. Compared with the controls, the casted limb of untreated dogs had half the bone mass and a twofold increase in bone PGE. Aspirin treatment was associated with a 65 percent reduction in bone PGE and a 13 percent bone mass sparing effect. These results provide indirect evidence that PGE plays a role in immobilization osteoporosis.