RS-23581, a synthetic analog of human PTH-related protein-(1-34), and the amino-terminal 34 amino acids of bovine PTH [bPTH-(1-34)] increase bone mineral density. We wished to determine how quickly the ultrastructure of the osteogenic cells, i.e. osteoblasts and lining cells, of the cancellous bone of the second lumbar vertebra of ovariectomized rats was altered in response to the initiation and cessation of treatment. Ovariectomized rats were injected daily with 80 micrograms/kg RS-23581, bPTH-(1-34), or vehicle for 19 days. Animals were killed throughout the treatment period and during the ensuing 10 days. By 5 days after the initiation of treatment with either peptide, the cells on the trabecular surface were predominantly (> 90%) osteoblasts, with only a small increase in the total cell number. Throughout the dosing period, the relative area of the cytoplasm of osteogenic cells from rats treated with RS-23581 or bPTH-(1-34) was greater than that of cells from the ovariectomized control group, suggesting a relationship between bone formation and cytoplasmic mass. By 7 days after the cessation of treatment, the trabecular surface was covered predominantly by lining cells without a change in cell number. Thus, these peptides apparently promote the osteoblast phenotype; the osteoblasts revert to lining cells after the peptides are withdrawn.