The effects of a diphosphonate, dichloromethylene diphosphonate (C12MDP) were studied using the rice rat as a model of periodontal bone loss. C12MDP was given in daily subcutaneous injections at dosages of 0 (control), 0.1, 1.0, or 10.0 mg/kg/day; these treatments were continued for periods of 6, 12, or 18 weeks. The amount of alveolar bone was increased over age matched controls at the 1.0 and 10.0 mg/kg/day doses at 6 weeks; at 12 and 18 weeks, all doses including 0.1 mg/kg/day showed increases in bone over controls. Due to increased connective tissue fibrosis, the CI2MDP treated animals had fewer vascular spaces. Also, the amount of destroyed tissue in the interdental test site was increased in animals given 10.0 mg/kg/day of C12MDP. The number of fibroblasts per mm of bone surface decreased slightly at 6 weeks, but was otherwise not different from controls in treated animals at 12 and 18 weeks. Numbers of osteoblasts decreased greatly at all doses at both 12 and 18 weeks time. There were no significant differences between treated and control animals in the number of osteoclast nuclei per mm bone surface. Also, the numbers of inflammatory cells residing at the bone surface increased at all time periods in the 10.0 mg/kg/day dose group. Finally, the proliferative activity of PDL fibroblasts decreased dramatically at all time periods in the 10.0 mg/kg/day dose group. The response of the proximal tibia to C12MDP was compared to the alveolar bone response in these animals by measuring amounts of bone in respective areas. While the dose response curves are similar, the tibiae showed greater increases in bone mass.