The effects of Prostaglandin E-2 (PGE-2) on cortical bone turnover in ribs and femurs of 32 intact adult dogs were evaluated following 3 months treatment. Static and dynamic histomorphometric skeletal changes were characterized using terminal in vivo tetracycline double labeling. PGE-2 caused a dose dependent increase in the formation of subperiosteal fibrous-lamellar new bone in femurs, and an increase in bone remodeling within the (original) cortical compacta of both femurs and ribs. Increased cortical remodeling resulted in a new steady state, but only in ribs. Increased Haversian remodeling in ribs and femurs was characterized by increases in the activation frequency, the number of bone resorbing and forming foci, the percent of osteons with single labels, and the radial closure and bone formation rates, with no effect on appositional rate. While the mean ratios of the number of resorption to formation foci (R/F) were unremarkable in femurs of treated versus control males, the R/F ratios in treated females were approximately 50% lower than matched controls. In treated males, both femoral osteon resorption and formation times were 50% shorter than matched controls. In treated females, femoral osteon resorption time was 2-4-fold shorter than the decrease in osteon formation time. Calcium and phosphorus levels were normal in all treated dogs. Serum alkaline phosphatase levels were increased approximately two-fold in high dose (10.0 mg/kg) dogs and correlated well with the histologic findings of increased skeletal turnover and bone formation.