Sixty-three patients with paralysis secondary to spinal cord injury (SCI) were screened for heterotopic ossification (HO) by bone scintigraphy 27 +/- 14 (mean +/- SD) days after SCI. There were four female and 59 male patients, 36 had paraplegia and 27 tetraplegia. The age of patients was 28 +/- 9 years. Bone scintigraphy was obtained with a 3-phase test using 99m-technetium labeled diphosphonate, and the positive third phase was used as a criterion for diagnosis of HO. Bone scintigraphy was negative for HO in 27 patients (14 tetraplegic and 13 paraplegic) and positive in 36 patients (13 tetraplegic and 23 paraplegic). The patients with positive HO were treated with etidronate, first with an intravenous dose of 300 mg/day for 3 days, and then with an oral dose of 20 mg/kg/day for 6 months. The follow-up of patients consisted of clinical and radiographic evaluations every 2-4 months. The extent of HO was classified radiographically. In the treated group of patients who completed the entire course of etidronate therapy one patient developed HO, the remaining 28 (97%) patients had no radiographic evidence of HO during the follow-up of 10.6 +/- 4.5 months after initiation of therapy. Our data indicate that: (a) early HO can be detected in the asymptomatic patients using bone scintigraphy on the average of 4 weeks (27 +/- 14 days) after SCI and (b) the therapy with etidronate might be effective in the prevention of HO in majority of patients when the treatment is initiated in an early stage of heterotopic bone formation.