Forty seven women with postmenopausal osteoporosis and at least one but no more than four vertebral compression fractures received sequential and cyclical therapy with phosphorus and etidronate (p/etid). During the same 2-year period of observation, three other groups of patients received either sodium fluoride (n = 12), estrogen replacement therapy (n = 12), or vitamin D and calcium (Ca++) alone (n = 15). Axial bone mineral density (BMD) was measured by means of dual-photon absorptiometry. Lateral thoracic and lumbar spine radiographs were taken to assess fractures. Bone mineral density increased from baseline during p/etid therapy: Mean 15.7 +/- 1.6% (SD) (P less than 0.001). During the same time, the patients in the sodium fluoride group showed a comparable increase in their BMD from baseline: mean 15.7 +/- 1.1% (P less than 0.001). During the first year of therapy, patients in the estrogen replacement group had an increase in their BMD from baseline: mean: 4.6% +/- 1.1% (P less than 0.05). No change in BMD was seen in the control group that received vitamin D and Ca++ alone. No patient who received p/etid, sodium fluoride, or estrogen replacement therapy had any new vertebral compression fractures or height loss, whereas in the control group that received vitamin D and Ca++ alone 6 out of 15 had height loss and at least one new vertebral fracture (P less than 0.01). p/etid therapy increases BMD in women with postmenopausal osteoporosis comparable to sodium fluoride but without side effects or toxicity and stabilizes vertebral compression fractures.