We have performed a study of the safety and efficacy of cyclic sequential oral phosphate, diphosphonate and calcium carbonate. Forty-two postmenopausal women with osteoporosis diagnosed by dual-photon absorptiometry were treated with a sequential cyclic regimen of oral phosphate for 3 days, etidronate for 2 wk, and then a calcium salt for 12 wk. This was repeated cyclically for 3 yr. They were rescanned after every two 101-day cycles. A control group of 20 patient receiving only the calcium salt was matched for age, time since menopause, race and sex. The group treated with cyclic phosphate, etidronate, and calcium regimen had 80% fewer fractures than the control group over 3 yr of follow-up. Significant response in halting bone mineral loss and increasing bone mineral density was seen in none of the controls but in 90% of treated patients' lumbar spine and 70%-80% of the three regions of the femoral neck examined.