Intravenous disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate (pamidronate disodium) was used to treat 39 patients (22 males and 17 females, age range 48-85 years) with symptomatic Paget's disease. Patients were stratified into three groups based on the biochemical severity of the disease as assessed by fasting urinary hydroxyproline excretion (HypE, mumol/liter GF, glomerular filtrate): group I (n = 23), HypE < 5.0, treated with 120 mg total dose over 2 or 4 days; group II (n = 6), 5.0 < or = HypE < or = 10.0, 180 mg over 3 or 6 days; and group III (n = 10), HypE > 10.0, 240 mg over 4 or 8 days. Bone mineral density (BMD) was measured before and 3 and 6 months following treatment in the spine (L1-4) using dual-energy x-ray absorptiometry and in the forearm at an ultradistal and a shaft site using single-photon absorptiometry. When groups I-III were combined, nonpagetic and pagetic lumbar spinal BMD had both risen significantly at 3 months compared with the pretreatment values (p < 0.001). In each group, lumbar spinal BMD in pagetic vertebrae rose markedly by 3 months, with no further significant change at 6 months. The percentage rises in the three groups were not different from each other at 3 or 6 months. Nonpagetic lumbar spinal BMD followed a similar and significant trend but with a significantly smaller rise than for pagetic bone. (For the combined groups, nonpagetic BMD rose 5.1 +/- 1.1% SEM, above pretreatment at 6 months; pagetic BMD rose 17.8 +/- 1.6%: significance of comparison = p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)