Bisphosphonates have been shown to increase bone mass in estrogen-deficient patients by inhibiting osteoclast activity. The purpose of this study was to measure clinical and radiographic effects of a bisphosphonate on periodontitis development in monkeys. Twenty-seven (27) adult cynomolgus monkeys were studied. After quarantine, baseline data were obtained including plaque index, gingival index, clinical probing depth measurements, and intraoral radiographs. Standardized radiographs were analyzed for quantitative changes in bone density using a computer assisted densitometric (CADIA) system. Animals were divided into 3 groups to receive 1 of the 3 treatment agents; these agents consisted of two levels of the test drug (alendronate) and a saline placebo. Agents were injected in the saphenous vein of the lower leg every 2 weeks for 16 weeks. One week after the initiation of treatment agent injections, mandibular right molars and premolars were ligated with 3-0 silk sutures to induce periodontitis. Ligated teeth were also inoculated with Porphyromonas gingivalis to insure a significant etiologic challenge. Nonligated homologous teeth served as controls. Clinical measurements and radiographs were repeated at 8 and 16 weeks after ligation. The bisphosphonate at a concentration of 0.05 mg/kg significantly retarded the progression of periodontitis as measured by bone density changes. The higher level dose of the test drug did not differ from placebo with respect to loss of bone density. Clinical indices were not affected significantly by the test drugs. Drugs that alter bone metabolism may offer a new approach to the treatment of periodontal disease.