A synthetic peptide corresponding to the N-terminal amino acid residues of stanniocalcin (STC1-20) and including a region that is known to be an active site in teleosts was prepared and tested for its effects on the metabolism of mammalian bone in vitro. STC1-20 (10(-10)-10(-12) M) inhibited increases in the number of tartrate-resistant acid phosphatase-positive, multinucleated cells promoted by an N-terminal fragment of human parathyroid hormone (hPTH1-34) in cultures of murine hemopoietic cells. STC1-20 also slightly decreased the rate of loss of radioactivity from calvariae of fetal rats that had been prelabeled with 45Ca, both with and without stimulation by hPTH1-34. The accumulation of cAMP induced by hPTH1-34 in ROS 17/2.8-5 cells was suppressed by STC1-20 (10(-10)-10(-12) M). Treatment with STC1-20 (10(-11)-10(-13) M) caused increases of the rate of incorporation of [3H]proline into the collagenase-digestible protein of calvariae in newborn mice. From these results, it appears that STC1-20 has diverse effects on the metabolism of mammalian bone, causing a biphasic response. Such effects have not been observed with intact stanniocalcin or with materials from the corpuscles of Stannius and they are also different from the effects of hPTH1-34.