The objective of this study was to determine whether intermittent synthetic human PTH-related protein (PTHrP 1-34) will mimic the anabolic effect of PTH and increase bone mass in rats. Dose response experiments were done on young, male Sprague-Dawley rats given sc vehicle, human (h) PTH (1-34) at 8 micrograms/100 g or PTHrP (1-34) at 1-32 micrograms/100 g daily for 12 days or 26 days. On the last day, 3 h after injections, rats were killed and serum, femurs, and tibias harvested. Trabecular and cortical bone of distal half femurs were analyzed for calcium (Ca) and hydroxyproline content and dry weight. Tibia metaphyseal bone was analyzed using conventional histomorphometry techniques. Our results showed that low doses of PTHrP (1-34) did not increase bone mass or bone forming surfaces. After 12 days, PTH, at 8 micrograms/100 g, increased trabecular Ca, dry weight, and hydroxyproline by approximately 19%, 36%, and 53%, respectively, while the bone mass of PTHrP-treated rats was comparable to vehicle-treated rats. PTHrP at a higher dose of 32 micrograms/100 g, increased trabecular bone mass by 30-37%, compared to the 43-48% increase induced by PTH at 8 micrograms/100 g after 12 days. When treatment was extended to 26 days, PTHrP, at 16 micrograms/100 g, increased trabecular bone mass by 24-36%, respectively, compared to the 43-61% increase induced by PTH at 8 micrograms/100 g. Unlike PTH, which increased cortical bone mass by 15-25%, PTHrP increased cortical bone mass only at the highest dose tested, 32 micrograms/100 g. Bone forming surfaces but not bone apposition rate were increased by PTH and PTHrP while resorption measures remained comparable to control values. Although serum Ca and Pi remained in the physiological range for all rats, the values for PTHrP-treated rats were consistently higher. In conclusion, PTHrP (1-34) was less potent and less effective than PTH (1-34) in inducing an anabolic response in bone in vivo.