The aim of this double-blind, randomized study was to compare the effects of two pamidronate dosages, given as repeated infusions in patients with advanced malignant osteolytic bone disease and bone pain. Seventy patients were randomly assigned to receive pamidronate 60 mg or 90 mg i.v. every 3 weeks for a maximum of six cycles. Pain parameters, analgesic consumption and performance status were assessed at baseline and throughout the study. Furthermore, total-body bone mineral density was measured using dual-energy X-ray absorptiometry at baseline, after three and after six infusions. Sixty percent (95% CI 41-77%) of the patients in the 60 mg group and 63% (95% CI 44-79%) of the patients in the 90-mg group had a sustained reduction of pain intensity and were classified as pain responders. Median duration of pain response was 15 versus 12 weeks in the 60-mg and 90-mg groups, respectively (P = 0.32). After two infusions, significant changes in pain intensity, pain frequency, general well-being and WHO pain score were observed (P<0.01). A trend toward improved performance status and reduced consumption of analgesics was also observed. Patients in the 90-mg group had more pronounced bone remineralization as measured by total-body bone mineral density. No significant difference was detectable between the two pamidronate treatments in any of the parameters evaluated. In conclusion, bone pain can be effectively reduced by repeated pamidronate infusions in patients with advanced osteolytic bone disease. Pamidronate 90 mg every 3 weeks results in higher bone remineralization, but this difference did not translate into a further increase of palliative effects.