Carboxyl-terminal peptides from parathyroid hormone-related protein (PTHrP) have been studied for their effect on bone resorption by osteoclasts isolated from 15 day embryonic chickens. Basal bone resorption by chicken osteoclasts was directly inhibited by chicken and human PTHrP-(107-139) and the pentapeptide PTHrP-(107-111). The chicken and human analogs were equipotent. Both the number of resorption pits and the total area resorbed per bone slice were reduced by PTHrP-(107-139), but it did not alter the size of individual resorption pits. Resorption stimulated by hPTH-(1-34) in cocultures of chicken osteoclasts with osteoblasts was also inhibited by cPTHrP-(107-139) but required a concentration three orders of magnitude greater than that required to inhibit basal resorption in cocultures or cultures of isolated osteoclasts. The finding of resorption inhibitory activity by PTHrP-(107-139) in avian as well as mammalian species strengthens the hypothesis that carboxyl-terminal PTHrP may act as a paracrine regulator of bone cell activity.